Comprehensive Physiology Wiley Online Library

Modulation of Cardiac Myofilament Activity by Protein Phosphorylation

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Modulation of Cardiac Myofilament Activity as A Physiological Regulatory Device
2 Major Functional Sarcomeric Proteins and the Transition from Diastole to Systole
2.1 Thin Filament Proteins in Diastole and Systole
2.2 Thick Filament Proteins in Diastole and Systole
2.3 Crossbridge and Thin Filament States in Diastole and in Systole
3 cTnI Function and Phosphorylation
3.1 Primary Structure of cTnI and Potential Sites of Phosphorylation
3.2 cTnI Protein Kinase A Sites
3.3 Functional Effects of Phosphorylation of cTnI by Protein Kinase A
3.4 cTnI Protein Kinase C Sites
3.5 Functional Effects of Phosphorylation of cTnI by Protein Kinase C
3.6 Integration of Signals for Cardiac Myocyte Hypertrophy/Failure with cTnI Protein Phosphorylation
4 cTnT Function and Phosphorylation
4.1 cTnT Primary Structure and Functional Domains
4.2 cTnT Sites of Phosphorylation
5 Tropomyosin Function and Phosphorylation
5.1 Tropomyosin isoforms and cardiac function
5.2 Tropomyosin Phosphorylation
6 MLC2 Function and Phosphorylation
6.1 Primary Structure of MLC2 and Functional Domains
6.2 Metal Binding to MLC2
6.3 MLC2 and Modulation of Striated Muscle Contraction
6.4 MLC2 Phosphorylation and Regulation of Crossbridges
7 Phosphorylation and Function of Cardiac Myosin Binding Protein C
7.1 Primary Structure of MyBP‐C and Functional Domains
7.2 Phosphorylation Sites of Cardiac MyBP‐C
8 Summary and Conclusions
Figure 1. Figure 1.

Structural units of the myofilaments in the diastolic and systolic state. Both panels show an edge of the thick filament with myosin heads (S1) extending toward the thin filament. The crossbridge is shown as comprised of the S1 portion of the myosin heavy chain with a globular head and a lever arm formed by an α‐helix that extends from the long tail making up the thick filament. Associated with the crossbridge are two light chains, MLC1 and MLC2. Associated with myosin is myosin binding protein C (MyBP‐C), which connects to titin, a structural protein. One MyBP‐C molecule is shown attached to the S2 region of myosin. Three such molecules may wrap around the thick filament. A. Diastole. In this state, Ca2+ is not bound to the regulatory site on troponin C (cTnC), cTnI is tethered to actin, and cTnT binds tightly to the actin‐Tm. This disposition of the thin‐filament proteins holds Tm and Tn in a position that physically blocks the actin‐myosin interaction and may also allosterically affect actin reactivity with myosin. B. Systole in which crossbridges are generating force. Ca2+‐binding to cTnC has triggered a reversal of the inhibited state of the thin filament and caused Tn and Tm to move on thin filament. Note that the bound crossbridge has moved Tm further on the thin filament than could have occurred with Ca2+ binding alone. The result is that the near‐neighbor crossbridge is shown reacting with actin in a force‐generating complex without Ca2+ bound to TnC. See text for further details.

Figure 2. Figure 2.

Actin domains and the three states of the myofilaments. Three actins are shown with an illustration of positions of Tm in the various states of the myofilaments. Striped domains and amino acid numbers indicate myosin binding regions. Numbers 1–4 indicate subdomains of actin, which themselves may move upon transition from the blocked to the open state.

Figure 3. Figure 3.

Schematic illustration of a myofilaments in the blocked, closed, and open states. These states are determined by the position of Tm and Tn on the thin filament, which, in the absence of Ca2+‐binding to cTnC, holds the crossbridges either in weakly attached (closed) state or physically hindered (blocked state) from reacting with actin in a force‐generating complex. Transition to the open, force‐generating state is promoted by Ca2+ binding to cTnC and interaction of the crossbridge with the thin filament.

Figure 4. Figure 4.

Schematic representation of a functional unit of the thin filament illustrating regional locations of sites of protein phosphorylation. During diastole, Ca2+ or Mg2+ is bound exclusively to the high‐affinity binding sites located in the C‐terminus of TnC. The near N‐terminus of cTnI is bound to the C‐termini of cTnT and cTnC. The inhibitory region of TnI (cross‐hatched region in the middle of TnI), is bound to actin‐tropomyosin as is a second actin binding site (residues 156–168 in the C‐terminus of cTnI). These interactions inhibit the actin–myosin force‐generating reaction. During systole, Ca2+ is bound to a single site in the N‐terminal domain of cTnC. This induces a conformational change in cTnC, which is transmitted through the thin filament proteins. There is a weakening in the interaction between TnI and actin‐Tm and a strengthening in the interaction between cTnI and cTnC as well as between cTnC and cTnT. This occurs in part because of a switch in binding of the cTnI inhibitory region from actin‐Tm to the C‐terminal half of TnC. These changes in thin filament conformation release the thin filament from its inhibited state and promote the force‐generating actin‐myosin reaction.



Figure 1.

Structural units of the myofilaments in the diastolic and systolic state. Both panels show an edge of the thick filament with myosin heads (S1) extending toward the thin filament. The crossbridge is shown as comprised of the S1 portion of the myosin heavy chain with a globular head and a lever arm formed by an α‐helix that extends from the long tail making up the thick filament. Associated with the crossbridge are two light chains, MLC1 and MLC2. Associated with myosin is myosin binding protein C (MyBP‐C), which connects to titin, a structural protein. One MyBP‐C molecule is shown attached to the S2 region of myosin. Three such molecules may wrap around the thick filament. A. Diastole. In this state, Ca2+ is not bound to the regulatory site on troponin C (cTnC), cTnI is tethered to actin, and cTnT binds tightly to the actin‐Tm. This disposition of the thin‐filament proteins holds Tm and Tn in a position that physically blocks the actin‐myosin interaction and may also allosterically affect actin reactivity with myosin. B. Systole in which crossbridges are generating force. Ca2+‐binding to cTnC has triggered a reversal of the inhibited state of the thin filament and caused Tn and Tm to move on thin filament. Note that the bound crossbridge has moved Tm further on the thin filament than could have occurred with Ca2+ binding alone. The result is that the near‐neighbor crossbridge is shown reacting with actin in a force‐generating complex without Ca2+ bound to TnC. See text for further details.



Figure 2.

Actin domains and the three states of the myofilaments. Three actins are shown with an illustration of positions of Tm in the various states of the myofilaments. Striped domains and amino acid numbers indicate myosin binding regions. Numbers 1–4 indicate subdomains of actin, which themselves may move upon transition from the blocked to the open state.



Figure 3.

Schematic illustration of a myofilaments in the blocked, closed, and open states. These states are determined by the position of Tm and Tn on the thin filament, which, in the absence of Ca2+‐binding to cTnC, holds the crossbridges either in weakly attached (closed) state or physically hindered (blocked state) from reacting with actin in a force‐generating complex. Transition to the open, force‐generating state is promoted by Ca2+ binding to cTnC and interaction of the crossbridge with the thin filament.



Figure 4.

Schematic representation of a functional unit of the thin filament illustrating regional locations of sites of protein phosphorylation. During diastole, Ca2+ or Mg2+ is bound exclusively to the high‐affinity binding sites located in the C‐terminus of TnC. The near N‐terminus of cTnI is bound to the C‐termini of cTnT and cTnC. The inhibitory region of TnI (cross‐hatched region in the middle of TnI), is bound to actin‐tropomyosin as is a second actin binding site (residues 156–168 in the C‐terminus of cTnI). These interactions inhibit the actin–myosin force‐generating reaction. During systole, Ca2+ is bound to a single site in the N‐terminal domain of cTnC. This induces a conformational change in cTnC, which is transmitted through the thin filament proteins. There is a weakening in the interaction between TnI and actin‐Tm and a strengthening in the interaction between cTnI and cTnC as well as between cTnC and cTnT. This occurs in part because of a switch in binding of the cTnI inhibitory region from actin‐Tm to the C‐terminal half of TnC. These changes in thin filament conformation release the thin filament from its inhibited state and promote the force‐generating actin‐myosin reaction.

References
 1. Abbott, M. B., V. Gaponenko, E. Abusamhadneh, N. Finley, G. Li, A. Dvoretsky, M. Rance, R. J. Solaro, and P. R. Rosevear. Regulatory domain conformational exchange and linker region flexibility in cardiac troponin C bound to cardiac troponin I. J. Biol. Chem. 275: 20610–206107, 2000.
 2. Akella, A. B., X. L. Ding, R. Cheng, and J. Gulati. Diminished Ca2+ sensitivity of skinned cardiac muscle contractility coincident with troponin T‐band shifts in the diabetic rat. Circ. Res. 76: 600–606, 1995.
 3. Al‐Hillawi, E. D., G. Bhandar, H. R. Trayer, and I. P. Trayer. The effects of phosphorylation of cardiac troponin‐I on its interactions with actin and cardiac troponin‐C. Eur. J. Biochem. 228: 962–970, 1995.
 4. Allen, D. G. and J. C. Kentish. The cellular basis of the lengthtension relation in cardiac muscle. J. Mol. Cell Cardiol. 2; 17: 821–840, 1985.
 5. Anderson, P. A. W., N. N. Malouf, A. Oakeley, E. D. Pagani, and P. D. Allen. Troponin T isoform expression in humans: a comparison among normal and failing adult heart, fetal heart, and adult and fetal skeletal muscle. Circ. Res. 60: 1226–1233, 1991.
 6. Anderson, P. A. A. Greig, T. M. Mark, N. N. Malouf, A. E. Oakeley, R. M. Ungerleider, P. D. Allen, and B. K. Kay. Molecular basis of human cardiac troponin T isoforms expressed in the developing, adult, and failing heart. Circ. Res. 76: 681–686, 1995.
 7. Andreev, O. A. and J. Borejdo. Interaction of the heavy and light chains of cardiac myosin subfragment‐1 with F‐actin. Circ. Res. 81: 688–693, 1997.
 8. Bagshaw, C. R., and G. H. Reed. The significance of the slow dissociation of divalent metal ions from myosin regulatory light chains. FEBS Lett. 81: 386–390, 1977.
 9. Bárány M. and K. Bárány. Protein phosphorylation in cardiac and vascular smooth muscle. Am. J. Physiol. 241 (Heart Circ. Physiol. 10): H117–H1128, 1981.
 10. Barsotti, R. and T. Butler. Chemical energy usage and myosin light chain phosphorylation in mammalian skeletal muscle. J. Muscle Res. Cell Motil. 5: 45–64, 1984.
 11. Bartel, S., B. Stein, T. Eschenhagen, U. Mende, J. Neumann, W. Schmitz, E. G. Krause, P. Karczewski, and H. Sholz. Protein phosphorylation in isolated trabeculae from nonfailing and failing human hearts. Mol. Cell. Biochem. 157: 171–179, 1996.
 12. Bodor, G., S. A. E. Oakely, P. D. Allen, D. L. Crimmins, J. H. Ladenson, and P. A. Anderson. Troponin I phosphorylation in the normal and failing adult human heart. Circulation 96: 1495–1500 1997.
 13. Bowling, N. R. A. Walsh, G. Song, T. Estridge, G. E. Sandusky, R. L. Fouts, K. Mintze, T. Pickard, R. Roden, M. R. Bristow, H. N. Sabbah, J. L. Mizrahi, G. Gromo, G. L. King, and C. J. Vlahos. Increased protein kinase C activity and expression of Ca2+‐sensitive isoforms in the failing human heart. Circulation 99: 384–91, 1999.
 14. Bowman, J. C., S. J. Steinberg, T. Jiang, D. L. Geenen, G. I. Fishman, and P. M. Buttrick. Expresson of protein kinase C beta in the heart causes hypertrophy in adult mice and sudden death in neonates. J. Clin Invest 100: 2189–2195, 1997.
 15. Bremel, R. D., J. M. Murray, and A. Weber. Manifestations of cooperative behavior in the regulated actin filament during actin activated ATP hydrolysis in the presence of calcium. Cold Spring Harbor Symp. Quant. Biol. 37: 267–275, 1972.
 16. Brenner, B. Effect of Ca2+ on cross‐bridge turnover kinetics in skinned single rabbit psoas fibers: implications for regulation of muscle contraction. Proc. Natl. Acad. Sci. U.S.A. 85: 3265–3269, 1988.
 17. Brietbart, R. E., and B. Nadal‐Ginard. Complete nucleotide sequence of the fast skeletal troponin T gene. Alternatively spliced exons exhibit unusual interspecies divergence. J. Mol. Biol. 188: 313–324, 1986.
 18. Capogrossi, M. C., T. Kaku, C. R. Filburn, D. J. Pelto, R. G. Hansford, H. A. Spurgeon, and E. G. Lakatta. Phorbol ester and dioctanoylglycerol stimulate membrane association of protein kinase C and have a negative inotropic effect mediated by changes in cytosolic Ca2+ in adult rat cardiac myocytes. Circ. Res. 66: 1143–1155, 1990.
 19. Carrier, L., G. Bonne, E. Bährend, B. Yu, P. Richard, F. Niel, B. Hainque, C. Cruaud, F. Gary, S. Labeit, J.‐B. Bouhour, O. Dubourg, M. Desnos, A. A. Hagège, R. J. Trent, M. Komajda, and K. Schwartz. Organization and sequence of human cardiac myosin binding protein C gene (MYBPC3) and identification of mutations predicted to produce truncated proteins in familial hypertrophic cardiomyopathy. Circ. Res. 80: 427–434, 1997.
 20. Chandra M., W.‐J. Dong, B.‐S. Pan, H. C. Cheung, and R. J. Solaro. Effects of protein kinase A phosphorylation on signaling between cardiac troponin I and the N‐terminal domain of cardiac troponin. C. Biochemistry 36: 13305–13311, 1997.
 21. Chandra, M., J. J. Kim, and R. J. Solaro. An improved method for exchanging troponin subunits in detergent skinned rat cardiac fiber bundles. Biochem. Biophys. Res. Commun. 263: 219–223, 1999.
 22. Chandra, M., D. E. Montgomery, J. J. Kim, and R. J. Solaro. The N‐terminal region of troponin T is essential for the maximal activation of rat cardiac myofilaments. J. Mol. Cell. Cardiol. 31: 867–880, 1999.
 23. Chong, P. C. S, and R. S. Hodges. Proximity of sulfhydryl groups to the sites of interaction between components of the troponin complex from rabbit skeletal muscle. J. Biol. Chem. 257: 2549–2555, 1982.
 24. Chong, P. C. S, and R. S. Hodges. Photochemical cross‐linking between rabbit skeletal troponin subunits. Troponin I‐troponin T interactions. J. Biol. Chem. 257: 11667–11672, 1982.
 25. Cingolani, H. E., B. V. Alvarez, I. L. Ennis, M. C. Camilion de Hurtado. Stretch‐induced alkalinization of the feline papillary muscle. An autocrine‐paracrine system. Circ. Res. 83: 775–780, 1998.
 26. Clement, O., M. Puceat, M. P. Walsh, and G. Vassort. Protein kinase C enhances myosin light‐chain kinase effects on force development and ATPase activity in rat single skinned cardiac cells. Biochem. J. 285: 311–317, 1992.
 27. Cole, H. A. and S. V. Perry. The phosphorylation of troponin I from cardiac muscle. Biochem. J. 149: 525–533, 1975.
 28. Colyer, J. and J. H. Wang. Dependence of cardiac sarcoplasmic reticulum calcium pump activity on the phosphorylation status of phospholamban. J. Biol. Chem. 266: 17486–17493, 1991.
 29. Cooke, R, Franks K, and J. T. Stull. Myosin phosphorylation regulates the ATPase activity of permeable skeletal muscle fibers. FEBS Lett. 144: 33–37, 1982.
 30. Crow, M. T. and M. J. Kushmerick. Myosin Light chain phosphorylation is associated with a decrease in the energy cost for contraction in fast twitch mouse muscle. J. Biol. Chem. 257: 2121–2124, 1982.
 31. D'Angelo, D. D., Y. Sakata, J. N. Lorenz, G. P. Boivin, R. A. Walsh, S. B. Liggett, and G. W. Dorn II. Transgenic Gαq over‐expression induces cardiac contractile failure in mice. Proc. Natl. Acad. Sci. U.S.A. 94: 8121–8126, 1997.
 32. Dalgarno, D. C., R. J. A. Grand, B. A. Levine, A. J. G. Moir, G. M. M. Scott, and S. V. Perry. Interaction between troponin I and troponin C. FEBS Lett. 149: 54–58, 1982.
 33. Dalla Libera, L., E. Hoffmann, M. Floroff, and G. Jackowski. Isolation and nucleotide sequence of the cDNA encoding human ventricular myosin light chain 2. Nucleic Acids Res. 17: 2360, 1989.
 34. Damron, D. S., A. Darvish, L. Murphy, W. Sweet, C. S. Moravec, and M. Bond. Arachidonic acid‐dependent phosphorylation of troponin I and myosin light chain 2 in cardiac myocytes. Circ. Res. 76: 1011–1019, 1995.
 35. de Belle, I. and A. S. Mak. Isolation and characterization of tropomyosin kinase from chicken embryo. Biochim Biophys Acta 925: 17–26, 1987.
 36. Diffee, G. M., J. R. Patel, F. C. Reinach, M. L. Greaser, and R. L. Moss. Altered kinetics of contraction in skeletal muscle fibers containing a mutant myosin regulatory light chain with reduced divalent cation binding. Biophys. J. 71: 341–50, 1996.
 37. Dohet, C., E. al‐Hillawi, I. P. Trayer, J. C. Ruegg. Reconstitution of skinned cardiac fibres with human recombinant cardiac troponin‐I mutants and troponin‐C. FEBS Lett. 377: 131–134, 1995.
 38. Dolmetsch, R. E., R. S. Lewis, C. C. Goodnow, and J. I. Healy. Differential activation of transcription factors induced by Ca2+ response amplitude and duration. Nature 386: 855–858, 1997.
 39. Dong, W.‐J., M. Chandra, J. Xing, M. She, R. J. Solaro, and H. C. Cheung. Phosphorylation‐induced distance change in a cardiac muscle Troponin I mutant. Biochemistry 36: 6754–6761, 1997.
 40. Dong, W.‐J., M. Chandra, J. Xing, R. J. Solaro, and H. C. Cheung. Conformation of the N‐terminal segment of a monocysteine mutant of Troponin I from cardiac muscle. Biochemistry 36: 6745–6753, 1997.
 41. Endoh, M. and J. R. Blinks. Actions of sympathomimetic amines on the Ca2+ transients and contractions of rabbit myocardium: reciprocal changes in myofibrillar responsiveness to Ca2+ mediated through α‐ and ã‐adrenoceptors. Circ. Res. 62: 247–265, 1988.
 42. England, P. J. Cardiac function and phosphorylation of contractile proteins. Phil. Trans. R. Soc. Lond. B 302: 83–90, 1983.
 43. Evans, C., J. R. Pena, M. Muthuchamy, D. F. Wieczorek, R. J. Solaro, and B. M. Wolska. Altered hemodynamics and response to ã‐adrenergic stimulation in transgenic mice harboring a mutant tropomyosin linked to hypertrophic cardiomyopathy. Am. J. Physiol. (Heart Circ. Physiol.) 279: H2414–24123, 2000.
 44. Farah, C. S. and F. C. Reinach. The troponin complex and regulation of muscle contraction. FASEB J. 9: 755–767, 1995.
 45. Farah, C. S., C. A. Miyamoto, C. H. I Ramos, A. R. da Silva, R. B. Quaggio, K. Fujimori, L. B. Smillie, and F. C. Reinach. Structural and regulatory functions of the NH2‐ and COOH‐terminal regions of skeletal muscle troponin I. J. Biol. Chem. 269: 5230–5240, 1994.
 46. Fentzke, R. C., S. H. Buck, J. R. Patel, H. Lin, B. M. Wolska, M. O. Stojanovic, A. M. Martin, R. J. Solaro, R. L. Moss, and J. M. Leiden. Impaired cardiomycyte relaxation and diastolic function in transgenic mice expressing slow skeletal troponin I in the heart. J. Physiol. (Lond.) 517: 143–157, 1999.
 47. Fisher, D., G. Wang, and L. S. Tobacman. NH2‐terminal truncation of skeletal muscle troponin T does not alter the Ca2+ sensitivity of thin filament assembly. J. Biol. Chem. 270: 25455–25460, 1995.
 48. Fougerousse, F., A. L. Delezoide, M. Y. Fiszman, K. Schwartz, J. S. Beckmann, and L. Carrier. Cardiac myosin binding protein C gene is specifically expressed in heart during murine and human development. Circ. Res. 82: 130–133, 1998.
 49. Freiburg, A. and M. Gautel. A molecular map of the interactions between titin and myosin‐binding protein C. Implications for sarcomeric assembly in familial hypertrophic cardiomyopathy. Eur. J. Biochem. 235: 317–23, 1996.
 50. Fuchs, F., Y.‐M. Liou and Z. Grabarek. The reactivity of sulfhydryl groups of bovine cardiac troponin C. J. Biol. Chem. 264: 20344–20349, 1989.
 51. Fürst, D. O., U. Vinkemeyer, and K. Weber. Mammalian skeletal muscle C‐protein: purification from bovine muscle, binding to titin and the characterization of a full‐length cDNA. J. Cell Sci. 102: 769–778, 1992.
 52. Gagne, S. M., S. Tsuca, M. X. Li, L. B. Smillie, and B. D. Sykes. Structure of the troponin C regulatory domains in the apo and calcium‐saturated states. Nature Struct Biol. 2: 784–789, 1995.
 53. Gao, L., J. M. Kennedy, and R. J. Solaro. Differential expression of TnI and TnT isoforms in rabbit heart during the perinatal period and during cardiovascular stress. J. Mol. Cell. Cardiol. 27: 541–550, 1995.
 54. Gaponenko, V., E. Abusamhadneh, M. B. Abbot, N. Finleyh, G. Gasmi‐Seabrook, R. J. Solaro, M. Rance, and P. R. Rosevear. Effects of troponin I phosphorylation on conformational exchange in the regulatory domain of cardiac troponin C. J. Biol. Chem. 274: 16681–16684, 1999.
 55. Garvey, J. E., E. G. Kranias, and R. J. Solaro. Phosphorylation of C‐protein, troponin I and phospholamban in isolated rabbit hearts. Biochem. J. 249: 709–714, 1988.
 56. Gautel, M., O. Zuffardi, A. Freiburg, S. Labeit. Phosphorylation switches specific for the cardiac isoform of myosin binding protein‐C: a modulator of cardiac contraction?. EMBO J. 14: 1952–1960, 1995.
 57. Gautel, M., D. O. Furst, A. Cocco and S. Schiaffino. Isoform transitions of the myosin binding protein C family in developing human and mouse muscles: lack of isoform transcomplementation in cardiac muscle. Circ. Res. 82: 124–129, 1998.
 58. Geeves, M. A., and S. S. Lehrer. Dynamics of the muscle thin filament regulatory switch: the size of the cooperative unit. Biophys. J. 67: 273–282, 1994.
 59. Gilbert, R., M. G. Kelly, T. Mikawa and D. A. Fischman. The carboxyl terminus of myosin binding protein C (MyBP‐C, C‐protein) specifies incorporation into the A‐band of striated muscle. J. Cell Sci. 109: 101–111, 1996.
 60. Golitsina, N., Y. An, N. J. Greenfield, L. Thierfelder, K. Iizuka, J. G. Seidman, C. E. Seidman, S. S. Lehrer, and S. E. Hitchcock‐DeGregori. Effects of two familial hypertrophic cardiomyopathy‐causing mutations on alpha‐tropomyosin structure and function. Biochemistry 36: 4637–4642, 1997.
 61. Greenfield, N. J., G. T. Montelione, R. S. Farid, and S. E. Hitchcock‐DeGregorio. The structure of the N‐terminus of striated muscle alpha‐tropomyosin in a chimeric peptide: nuclear magnetic resonance structure and circular dichroism studies. Biochemistry 37: 7834–7843, 1998.
 62. Gruen, M. and M. Gautel. Cardiomyopathy (FHC) mutations in beta‐myosin S2 that cause familial Hypertrophic cardiomyopathy abolish the interaction with the regulatory domain of myosin‐binding protein‐C. J. Mol. Biol. 286: 933–949, 1999.
 63. Gruver, C. I., F. De Mayo, M. A. Goldstein, and A. R. Means. Targeted developmental overexpresson of calmodulin induces proliferative and hypertrophic growth of t cardiomyocytes in transgenic mice. Endocrinology 133: 376–388, 1993.
 64. Gu, X. and S. P. Bishop. Increased proein kinase C and isozyme redistribution in pressure‐overloaded cardaic hypertophy in the rat. Circ. Res. 75: 926–931, 1994.
 65. Guo, X., J. Wattanapermpool, K. A. Palmiter, A. M. Murphy, and R. J. Solaro. Mutagenesis of cardiac troponin I: role of the unique NH2‐terminal peptide in myofilament activation. J. Biol. Chem. 269: 15210–15216, 1994.
 66. Gusev, N. B., A. B. Dobrovolskii, and S. E. Severin. Isolation and some properties of troponin T kinase from rabbit skeletal muscle. Biochem. J. 189: 219–226, 1980.
 67. Gwathmey, J. K. and R. J. Hajar. Effect of protein kinase C activation on sarcoplasmic reticulum function and apparent myofibrillar Ca2+ sensitivity in intact and skinned muscles from normal and diseased human myocardium. Circ. Res. 67: 744–652, 1990.
 68. Hartzell, H. C. and W. S. Sale. Structure of C protein purified from cardiac muscle. J. Cell Biol. 100: 208–215, 1985.
 69. Hartzell, C. and D. Glass. Phosphorylation of purified cardiac muscle protein by purified cAMP‐dependent and endogenous Ca‐calmodulin‐dependent protein kinases. J. Biol. Chem. 259: 15587–15596, 1984.
 70. Hartzell, C. Phosphorylation of C protein in intact amphibian heart muscle. J. Mol. Biol. 186: 185–195, 1985.
 71. Hartzell, H. C. Effects of phosphorylation and unphosphorylated C‐protein on cardiac actomyosin ATPase. J. Mol. Biol. 186: 185–195, 1985.
 72. Hartzell, H. C. and L. Titus. Effects of cholinergic and adrenergic agonists on phosphorylation of a 165,000‐dalton myofibrillar protein in intact cardiac muscle. J. Biol. Chem. 257: 2111–2120, 1982.
 73. Hartzell, H. C. Phosphorylation of C‐protein in intact amphibian cardiac muscle. Correlation between 32P incorporation and twitch relaxation. J. Gen. Physiol. 83: 563–588, 1984.
 74. Heeley, D. H., L. B. Smillie, E. M. Lohmeier‐Vogel. Effects of deletion of tropomyosin overlap on regulated actomyosin subfragment 1 ATPase. Biochem. J. 258: 831–836, 1989.
 75. Heeley, D. H. Investigation of the effects of phosphorylation of rabbit striated muscle alpha alpha‐tropomyosin and rabbit skeletal muscle troponin‐T. Eur. J. Biochem. 221: 129–37, 1994.
 76. Heeley, D. H., M. H. Watson, A. S. Mak, P. Dubord, and L. B. Smillie. Effect of phosphorylation on the interaction and functional properties of rabbit striated muscle alpha alpha‐tropomyosin. J. Biol. Chem. 264: 2424–430, 1989.
 77. Heely, D. H., K. Golosinska, L. B. Smillie. The effects of troponin T fragments T1 and T2 on the binding of nonpolymerizable tropmyosin to F‐actin in the presence and absence of troponin I and troponin C. J. Biol. Chem. 262: 9971–9978, 1987.
 78. High, C. W., and J. T. Stull. Phosphorylation of myosin in perfused rabbit and rat hearts. Am. J. Physiol. 239 (Heart Circ. Physiol. 8): H756–H764, 1980.
 79. Hitchcock‐De Gregori, S. E. Study of the structure of troponin‐I by measuring the relative reactivities of lysines with acetic anhydride. J. Biol. Chem. 257: 7372–7380, 1982.
 80. Hitchcock‐DeGregori, S. E. and Y. An. Integral repeats and a continuous coiled coil are required for binding of striated muscle tropomyosin to the regulated actin filament. J. Biol. Chem. 271: 3600–3603, 1996.
 81. Hoffman, P. A. and J. H. Lange III. Effect of phosphorylation of troponin I and C protein on isometric tension and velocity of unloaded shortening in skinned single cardiac myocytes from rats. Circ. Res. 74: 718–726, 1995.
 82. Hofmann, P., A. J. M. Metzger, M. L. Greaser, and R. L. Moss. Effects of partial extraction of light chain 2 on the Ca2+ sensitivities of isometric tension, stiffness, and velocity of shortening in skinned skeletal muscle fibers. J. Gen. Physiol. 95: 477–498, 1990.
 83. Hofmann, P. A., M. L. Greaser, and R. L. Moss. C‐protein limits shortening velocity of rabbit skeletal muscle fibres at low levels of Ca2+ activation. J. Physiol. (Lond.) 439: 701–715, 1991.
 84. Hofmann, P. A., H. C. Hartzell, and R. L. Moss. Alterations in Ca2+ sensitive tension due to partial extraction of C‐protein from rat skinned cardiac myocytes and rabbit skeletal muscle fibers. J. Gen. Physiol 97: 1141–1163, 1991.
 85. Hoh, J. F., G. H. Rossmanith, L. J. Kwan, and A. M. Hamilton. Adrenaline increases the rate of cycling of crossbridges in rat cardiac muscle as measured by pseudo‐random binary noise‐modulated perturbation analysis. Circ. Res. 62: 452–461, 1988.
 86. Hoit, B. D., E. G. Khoury, E. G. Kranias, N. Ball, and R. A. Walsh. In vivo echocardiographic detection of enhanced left ventricular function in gene‐targeted mice with phospholamban deficiency. Circ. Res. 77: 632–637, 1995.
 87. Holmes, K. C., D. Popp, W. Gebhard, and W. Kabsch. Atomic model of the actin filament. Nature 347: 44–49, 1990.
 88. Holroyde, M. J., E. Howe, R. J. Solaro. Modification of calcium requirements for activation of cardiac myofibrillar ATP‐ase by cAMP dependent phosphorylation. Biochim. Biophys. Acta. 586: 63–69, 1979.
 89. Holroyde, M. J., J. D. Potter, and R. J. Solaro. The calcium binding properties of phosphorylated and unphosphorylated cardiac skeletal myosins. J. Biol. Chem. 254: 6478–6482, 1979.
 90. Holroyde, M. J., D. A. Small, E. Howe, and R. J. Solaro. Isolation of cardiac myofibrils and myosin light chains with in vivo levels of light chain phosphorylation. Biochim. Biopys. Acta 587: 628–637, 1979.
 91. Hopkins, S. C., C. Sabido‐David, J. E. Corrie, M. Irving, and Y. E. Goldman. Fluorescence polarization transients from rhodamine isomers on the myosin regulatory light chain in skeletal muscle fibers. Biophys. J. 74: 3093–110, 1998.
 92. Huxley, H. E. Structural changes in the actin‐ and myosin‐containing filaments during contraction. Cold Spring Harbor Symp. Quant. Biol. 37: 361–376, 1972.
 93. Irving, M., T. St Claire Allen, C. Sabido‐David, J. S. Craik, B. Brandmeier, J. Kendrick‐Jones, J. E. Corrie, D. R. Trentham, and Y. E. Goldman. Tilting of the light‐chain region of myosin during step length changes and active force generation in skeletal muscle. Nature 375: 688–691, 1995.
 94. Iwasa, T., N. Inoue, K. Fukunaga, T. Isobe, T. Okuyama, and E. Miyamoto. Purification and characterization of a multifunctional calmodulin‐dependent protein kinase from canine myocardial cytosol. Arch. Biochem. Biophys. 248: 21–29, 1986.
 95. Janssen, P. M. L., and P. P. de Tombe. Protein kinase A does not alter unloaded velocity of sarcomere shortening in skinned rat cardaic trabeculae. Am. J. Physiol. 273 (Heart Circ. Physiol. 42): H2415–H2422, 1997.
 96. Jaquet, K., K. Fukunaga, E. Miyamoto, and H. E. Meyer. A site phosphorylated in bovine cardiac troponin T by cardiac CaM kinase II. Biochim. Biophys. Acta 1248: 193–195, 1995.
 97. Jeacocke, S. A., and P. J. England. Phosphorylation of a myofibrillar protein of Mr 150 000 in perfused rat heart, and the tentative indentification of this as C‐protein. FEBS Lett. 122: 129–132, 1980.
 98. Jha, P. K., P. C. Leavis, and S. Sarkar. Interaction of deletion mutants of troponin I and T: COOH‐terminal truncation of troponin T abolishes troponin I binding and reduces Ca2+‐sensitivity of reconstituted regulatory system. Biochemistry 35: 16573–16580, 1996.
 99. Jideama, N. M., T. A. Noland Jr Raynor, R. L., Blobe, G. C., Fabbro, D. Kazanietz, M. G., Blumberg, P. M., Hannun, Y. A., and J. F. Kuo. Phosphorylation specificities of protein kinase C isozymes for bovine cardiac troponin I and troponin T and sites within these proteins and regulation of myofilament properties. J. Biol. Chem. 271: 23277–23283, 1996.
 100. Johns, E. C., S. J. Simnett, I. P. Mulligan and C. C. Ashley. Troponin I phosphorylation does not increase the rate of relaxation following laser flash photolysis of dizo‐2 in guinea‐pig skinned trabeculae. Pflugers Arch. 433: 842–844, 1997.
 101. Johnson, J. A. and D. Mochly‐Rosen. Inhibition of the spontaneous rate of contraction of neonatal cardiac myocytes by protein kinase C isozymes. A putative role for the ɛ isozyme. Circ. Res. 76: 654–663, 1995.
 102. Kabsch, W., H. G. Mannherz, D. Suck, E. F. Pai and K. C. Homes. Atomic structure of the actin:DNase I complex. Nature 347: 37–44, 1990.
 103. Karczewski, P., S. Bartel, and E.‐G. Krause. Differential sensitivity to isoprenaline of troponin I and phospholamban phosphorylation in isolated rat hearts. Biochem. J. 266: 115–122, 1990.
 104. Katoh, N., B. C. Wise, and J. F. Kuo. Phosphorylation of cardiac troponin inhibitory subunit (troponin I) and tropomyosin‐binding subunit (troponin T) by cardiac phospholipid‐sensitive Ca2+‐dependent protein. Biochem. J. 209: 189–195, 1983.
 105. Kleerekoper, Q, J. W. Howarth, X. Guo, R. J. Solaro, and P. R. Rosevear. Cardiac troponin I induced conformational changes in cardiac troponin C as monitored by NMR using site‐directed spin and isotope labeling. Biochemistry 34: 13343–13352, 1995.
 106. Kobayahsi, T., T. Tao, J. Gergely, and J. H. Collins. Structure of the troponin complex. J. Biol. Chem. 269: 5725–5729, 1994.
 107. Konhilas, J., B. M. Wolska, A. F. Martin, R. J. Solaro, and P. P. de Tombe. PKA modulates length dependent activation in murine myocardium. Biophys. J. 78: 108A, 2000.
 108. Komukai, K., and S. Kurihara. Length dependence of Ca2+‐tension relationship in aequorin‐injected ferret papillary mucles. Am. J. Physiol. 273 (Heart Circ. Physiol. 42): H10068–H10074, 1997.
 109. Korman, V. L., and L. S. Tobacman. Mutations in action subdomain 3 that impair their filament regulation by troponin and tropomyosin. J. Biol. Chem. 274: 22191–22196, 1999.
 110. Kraft, T., J. M. Chalovich, L. C. Yu, and B. Brenner. Parallel inhibition of active force and relaxed fiber stiffness by caldesmon fragments at physiological ionic strength and temperature conditions: additional evidence that weak cross‐bridge binding to actin is an essential intermediate for force generation. Biophys. J. 68: 2404–2418, 1995.
 111. Kranias, E. G., and R. J. Solaro. Phosphorylation of troponin I and phospholamban during catecholamine stimulation of rabbit heart. Nature 298: 182–184, 1982.
 112. Kranias, E. G. Regulation of calcium transport by protein phosphatase activity associated with cardiac sarcoplasmic reticulum. J. Biol. Chem. 260: 11006–11010, 1985.
 113. Kranias, E. G., J. L. Garvey, R. D. Srivastava, and R. J. Solaro. Phosphorylation and functional modifications of sarcoplasmic reticulum and myofibrils in isolated rabbit hearts stimulated with isoprenaline. Biochem. J. 226: 113–121, 1985.
 114. Kress, M., H. E. Huxley, A. R. Faruqi, and J. Hendrix. Structural changes during activation of frog muscle studied by time resolved X‐ray diffraction. J. Mol. Biol. 188: 325–342, 1986.
 115. Krudy, G., Q. Kleerekoper, X. Guo, J. W. Howarth, R. J. Solaro, and P. R. Rosevear. NMR studies delineating spatial relationships within the cardiac troponin I‐troponin C complex. J. Biol. Chem. 269: 23731–23735, 1994.
 116. Labeit, S., M. Gautel, A. Lakey, and J. Trinick. Towards a molecular understanding of titin. EMBO J. 11: 1711–1716, 1992.
 117. Lehman, W., P. Vibert, P. Uman, and R. Craig. Steric‐blocking by tropomyosin visualized in relaxed vertebrate muscle thin filaments. J. Mol. Biol. 251: 191–196, 1995.
 118. Lehman, W., R. Craig, and P. Vibert. Ca2+‐induced tropomyosin movement Limulus thin filaments revealed by three‐dimensional reconstruction. Nature 368: 65–67, 1994.
 119. Lehrer, S. The regulatory switch of the muscle thin filament: Ca2+ or myosin heads?. J. Muscle Res. Cell Motil. 15: 232–236, 1994.
 120. Lehrer, S. S., and M. A. Geeves. The muscle thin filament as a classical cooperative/allosteric regulatory system. J. Mol. Biol. 277: 1081–1089, 1998.
 121. Lehrer, S. S., and A. Yuan. The stability of tropomyosin at acid pH: effects of anion binding. J. Struct. Biol. 122: 176–179, 1998.
 122. Lehrer, S. S., N. L. Golitsina, and M. A. Geeves. Actin‐tropomyosin activation of myosin subfragment 1 ATPase and thin filament cooperativity. The role of tropomyosin flexibility and end‐to‐end interactions. Biochemistry 36: 13449–13454, 1997.
 123. Lester, J. W., K. F. Gannaway, R. A. Reardon, L. D. Koon, and P. A. Hofmann. Effects of adenosine and protein kinase C stimulation on mechanical properties of rat cardiac myocytes. Am. J. Physiol. 271 Heart Circ. Physiol. 40): H1778–H1785, 1996.
 124. Lesyzk, J., Z. Grabarek, J. Gergely, and J. H. Collins. Characterization of zero‐length cross‐links between rabbit skeletal muscle troponin C and troponin I: evidence for direct interaction between the inhibitory region of troponin I and the NH2‐terminal, regulatory domain of troponin C. Biochemistry 29: 299–304, 1990.
 125. Leszyk, J., R. Dumaswala, J. D. Potter, N. B. Gusev, A. D. Verin, L. S. Tobacman, and J. H. Collins. Bovine cardiac troponin T: amino acid sequences of the two isoforms. Biochemistry 26: 7035–42, 1987.
 126. Leszyk, J., J. H. Collins, P. C. Leavis, and T. Tao. Cross‐linking of rabbit skeletal muscle troponin subunits: labeling of cysteine‐98 of troponin‐C with 4‐maleimidobenzophenone and analysis of products formed in the binary complex with troponins I and. T. Biochemistry 27: 6983–6987, 1988.
 127. Levine, R. J., Z. Yang, N. D. Epstein, L. Fananapazir, J. T. Stull, and H. L. Sweeney. Structural and functional responses of mammalian thick filaments to alterations in myosin regulatory light chains. J. Struct. Biol. 122: 149–61, 1998.
 128. Levine, R. J., R. W. Kensler, Z. Yang, J. T. Stull, and H. L. Sweeney. Myosin light chain phosphorylation affects the structure of rabbit skeletal muscle thick filaments. Biophys. J. 71: 898–907, 1996.
 129. Li, L., J. Desantiago, G. Chu, E. G. Kranias, and D. M. Bers. Phosphorylation of phospholamban and troponin I in beta‐adrenergic‐induced acceleration of cardiac relaxation. Am. J. Physiol. 278 (Heart Circ. Physiol. 47): H769–H779, 2000.
 130. Lim, M., and M. Walsh. Phosphorylation of skeletal and cardiac muscle C‐proteins by the catalytic subunit of cAMP‐dependent protein kinase. Biochem. Cell Biol. 64: 622–630, 1986.
 131. Lindemann, J. P., L. R. Jones, D. R. Hathaway, B. G. Henry, and A. M. Watanabe. ã‐adrenergic stimulation of phospholamban phosphorylation and Ca2+‐ATPase activity in guinea pig ventricles. J. Biol. Chem. 258: 464–471, 1983.
 132. Lokuta, A. J., T. B. Rogers, W. J. Lederer, and H. H. Valdivia. Modulation of cardiac ryanodine receptors of swine and rabbit by a phosphorylation‐dephosphorylation mechanism. J. Physiol. (Lond.) 487: 609–622, 1995.
 133. Lorenz, M., K. J. V. Poole, D. Popp, G. Rosenbaum, and K. C. Holmes. An atomic model of the unregulated thin filament obtained by X‐ray fiber diffraction on oriented actin‐tropomyosin gels. J. Mol. Biol. 246: 108–119, 1995.
 134. Luo, W., I. L. Grupp, J. Harrer, S. Ponniah, G. Grupp, J. J. Duffy, T. Doetschman, and E. G. Kranias. Targeted ablation of the phospholamban gene is associated with markedly enhanced myocardial contractility and loss of ã‐agonist stimulation. Circ. Res. 75: 401–409, 1994.
 135. Mak, A. S., and L. B. Smillie. Structural interpretation of the two‐site binding of troponin on the muscle thin filament. J. Mol. Biol. 149: 541–550, 1981.
 136. Maytum, R., S. S. Lehrer, and M. A. Geeves. Cooperativity and switching within the three‐state model of muscle regulation. Biochemistry 38: 1102–1110, 1999.
 137. Mak, A. S., L. B. Smillie, and G. R. Stewart. Comparison of the amino acid sequences of rabbit skeletal muscle α‐ and ã‐tropomyosin. J. Biol. Chem. 255: 3649–3655, 1980.
 138. Malhotra, A., A. Nakouzi, J. Bowman, and P. Buttrick. Expression and regulation of mutant forms of cardiac TnI in a reconstituted actomyosin system: role of kinase dependent phosphorylation. Mol. Cell. Biochem. 170: 99–107, 1997.
 139. Malhotra, A., D. Reich, A. Nakouzi, V. Sanghi, D. L. Geenen, and P. M. Buttrick. Experimental diabetes is associated with functional activation of protein kinase C epsilon and phosphorylation of troponin I in the heart, which are prevented by angiotensin II receptor blockade. Circ. Res. 81: 1027–1033. 40, 1997a.
 140. Martin, A. M., K. Ball, L. Gao, P. K. Kumar, and R. J. Solaro. Identification and functional significance of troponin I isoforms in neonatal rat heart myofibrils. Circ. Res. 69: 1244–1252, 1991.
 141. McAuliffe, J. J., L. Gao, and R. J. Solaro. Changes in myofibrillar activation and troponin C Ca2+‐binding associated with troponin T isoform switching in developing rabbit heart. Circ. Res. 66: 1204–1216, 1990.
 142. McKillop, D. F., and M. A. Geeves. Regulation of the interaction between actin and myosin subfragment 1: evidence for three states of the thin filament. Biophys. J. 65: 693–701, 1993.
 143. McLachlan, A. D., and M. Stewart. The 14‐fold periodicity in α‐tropomyosin and the interaction with actin. J. Mol. Biol. 103: 271–298, 1976.
 144. McClellan, G., A. Weisberg, and S. Winegrad. cAMP can raise or lower cardiac actomyosin ATPase activity depending on alpha‐adrenergic activity. Am. J. Physiol. 267 (Heart Circ. Physiol. 36): H431–H442, 1994.
 145. McLachlan, A. D., and M. Stewart. The 14‐fold periodicity in alpha‐tropomyosin and the interaction with actin. J. Mol. Biol. 103: 271–298, 1976.
 146. McLachlan, A. D., and M. Stewart. Tropomyosin coiled‐coil interactions: evidence for an unstaggered structure. J. Mol. Biol. 98: 293–304, 1975.
 147. Mesnard, L., D. Logeart, S. Taviaux, S. Diriong, J. J. Mercadier, and F. Samson. Human cardiac troponin T: cloning and expression of new isoforms in the normal and failing heart. Circ. Res. 76: 687–692, 1995.
 148. Mesnard‐Rouiller, L., J. J. Mercadier, G. Butler‐Browne, M. Heimburger, D. Logeart, P. D. Allen, and F. Samson. Troponin T mRNA and protein isoforms in the human left ventricle: pattern of expression in failing and control hearts. J. Mol. Cell. Cardiol. 29: 3043–3055, 1997.
 149. Metzger, J. M., M. L. Greaser, and R. L. Moss. Variations in cross‐bridge attachment rate and tension with phosphorylation of myosin in mammalian skinned skeletal muscle fibers. Implications for twitch potentiation in intact muscle. J. Gen. Physiol. 93: 855–883, 1989.
 150. Metzger, J. M., and R. L. Moss. Myosin light chain 2 modulates calcium‐sensitive cross‐bridge transitions in vertebrate skeletal muscle. Biophys. J. 63: 460–468, 1992.
 151. Milligan, R. A., and P. F. Flicker. Structural relationships of actin, myosin, and tropomyosin revealed by cryo‐electron microscopy. J. Cell Biol. 105: 29–39, 1987.
 152. Milligan, R. A., M. Whittaker, and D. Safer. Molelcular structure of F‐actin and location of surface binding sites. Nature 348: 217–221, 1990.
 153. Mittmann, K., K. Jaquet, and L. M. G. Heilmeyer Jr. Ordered phosphorylation of a duplicated minimal recognition motif for cAMP‐dependent protein kinase present in cardiac troponin I. FEBS Lett. 302: 133–137, 1992.
 154. Mohamed, A. S., J. D. Dignam, and K. K. Schlender. Cardiac myosin‐binding protein C (MyBP‐C): identification of protein kinase A and protein kinase C phosphorylation sites. Arch. Biochem. Biophys. 358: 313–319, 1998.
 155. Moos, C., C. M. Mason, J. M. Besterman, I. N. M. Feng, and J. H. Dubin. The binding of skeletal muscle C‐protein to F‐actin and its relation to the interaction of actin with myosin. J. Mol. Biol. 124: 571–586, 1978.
 156. Molkentin, J. D., J.‐R. Lu, C. Antos, B. Markham, J. Richardson, J. Robbins, S. R. Grant, and E. N. Olson. A calcineurin‐dependent transcriptional pathway for cardiac hypertrophy. Cell 93: 215–228, 1998.
 157. Montgomery, K., and A. S. Mak. In vitro phosphorylation of tropomyosin by a kinase from chicken embryo. J. Biol. Chem. 259: 5555–5560, 1984.
 158. Moore, R. T., and J. T. Stull. Myosin light chain phosphorylation in fast and slow skeletal muscles in situ. Am. J. Physol. 247 (Cell Physiol. 16): C462–C471, 1984.
 159. Moos, C. and I. N. M. Feng. Effect of C‐protein on actomyosin ATPase. Biochem. Biophys. Acta 632: 141–149, 1980.
 160. Morano, I., F. Hofmann, M. Zimmer, and J. C. Ruegg. The influence of P‐light chain phosphorylation by myosin light chain kinase on the calcium sensitivity of chemically skinned heart fibres. FEBS Lett. 189: 221–224, 1985.
 161. Morano, I., O. Ritter, A. Bonz, T. Timek, C. F. Vahl, and G. Michel. Myosin light chain‐actin interaction regulates cardiac contractility. Circ. Res. 76: 720–725, 1995.
 162. Morano, I., M. Wankerl, M. Bohm, E. Erdmann, and J. C. Ruegg. Myosin P‐light chain isoenzymes in the human heart: evidence for diphosphorylation of the atrial P‐LC form. Basic. Res. Cardiol. 84: 298–305, 1989.
 163. Morimoto, K. and W. F. Harrington. Evidence for structural changes in vertebrate thick filament induced by calcium. J. Mol. Biol. 88: 693–709, 1974.
 164. Morris, E. P. and S. S. Lehrer. Troponin‐tropomyosin interactions. Fluorescence studies of the binding of troponin, troponin T and chymotryptic troponin T fragments to specifically labeled tropomyosin. Biochemistry 23: 2214–2320, 1984.
 165. Moss, R. L., J. D. Allen, and M. L. Greaser. Effects of partial extraction of troponin complex upon the tension∼pCa relation in rabbit skeletal muscle. Further evidence that tension development involves cooperative effects within the thin filament. J. Gen. Physiol. 87: 761–774, 1986.
 166. Moss, R. L. Ca2+ regulation of mechanical properties of striated muscle: mechanistic studies using extraction and replacement of regulatory proteins. Circ. Res. 70: 865–884, 1992.
 167. Moss, R. L., L. O. Nwoye, and M. L. Greaser. Substituion of cardiac troponin C into rabbit muscle does not alter the length dependence of Ca2+ sensitivity of tension. J. Physiol. 440: 273–289, 1991.
 168. Muthuchamy, M., I. Grupp, G. Grupp, B. O'Toole, A. Kier, G. Bolvin, J. Neumann, and D. Wieczorek. Molecular and physiological effects of overexpressing striated muscle betatropomyosin in the adult murine heart. J. Biol. Chem. 270: 30593–30603, 1995.
 169. Ngai, S.‐M., and F. D. Sönnichsen, R. S. Hodges. Photochemical cross‐linking between native rabbit skeletal troponin C and benzoyl‐troponin I inhibitory peptide residues 104–115. J. Biol. Chem. 269: 2798–2802, 1994.
 170. Ngai, S.‐M., and R. S. Hodges. Biologically important interactions between synthetic peptides of the N‐terminal region of troponin I and troponin C. J. Biol. Chem. 267: 15715–15720, 1992.
 171. Noland, T. A. Jr., R. L. Raynor, and J. F. Kuo. Identification of sites phosphorylated in bovine cardiac troponin I and troponin T by protein kinase C and comparative substrate activity of synthetic peptides containing the phosphorylation sites. J. Biol. Chem. 264: 20778–20785, 1989.
 172. Noland, T. A., X. Guo, R. L. Raynor, V. Averyhart‐Fullard, N. M. Jideama, R. J. Solaro, and J. F. Kuo. Cardiac troponin I mutants: phosphorylation by protein kinases C and A and regulation of Ca2+‐stimulated MgATPase of reconstituted actomyosin S‐1. J. Biol. Chem. 43: 25445–25454, 1995.
 173. Noland, T. A. Jr, and J. F. Kuo. Protein kinase C phosphorylation of cardiac troponin I and troponin T inhibits Ca2+‐stimulated MgATPase activity in reconstituted actomyosin and isolated myofibrils, and decreases actin‐myosin interactions. J. Mol. Cell. Cardiol. 25: 53–65, 1993.
 174. Noland, T. A. and J. F. Kuo. Phosphorylation of cardiac myosin light chain 2 by protein kinase C and myosin light chain kinase increases Ca2+‐stimulated actomyosin ATPase activity. Biochem. Biophy. Res. Commun. 193: 254–260, 1993b.
 175. Noland, T. A. Jr, and J. F. Kuo. Protein kinase C phosphorylation of cardiac troponin T decreases Ca2+‐dependent actomyosin MgATPase activity and troponin T binding to tropomyosin‐F‐actin complex. Biochem. J. 288: 123–129, 1992.
 176. Noland, T. A. Jr., R. L. Raynor, and J. F. Kuo. Identification of sites phosphorylated in bovine cardiac troponin I and troponin T by protein kinase C and comparative substrate activity of synthetic peptides containing the phosphorylation sites. J. Biol. Chem. 264: 20778–20785, 1989.
 177. Noland, T. A. Jr., R. L. Raynor, N. M. Jideama, X. Guo, M. G. Kazanietz, P. M. Blumberg, R. J. Solaro, and J. F. Kuo. Differential regulation of cardiac actomyosin S‐1 MgATPase by protein kinase C isozyme‐specific phosphorylation of specific sites in cardiac troponin I and its phosphorylation site mutants. Biochemistry 35: 14923–14931, 1996.
 178. Noland, T. A. Jr., and J. F. Kuo. Protein kinase C phosphorylation of cardiac troponin I or troponin T inhibits Ca2+‐stimulated actomyosin MgATPase activity. J. Biol. Chem. 266: 4974–4978, 1991.
 179. Noland, T. A., Jr., X. Guo, R. L. Raynor, N. M. Jedeama, V. Averyhart‐Fullard, R. J. Solaro, and J. F. Kuo. Cardiac troponin I mutants. Phosphorylation by protein kinases C and A and regulation of Ca2+‐stimulated MgATPase of reconstituted actomyosin S‐1. J. Biol. Chem. 43: 25445–25454, 1995.
 180. Offer, G. C‐protein and peridicity in the thick filaments of vertebrate skeletal muscle. Cold Spring Harbor Symp. Quant. Biol. 37: 87–93, 1972.
 181. Offer, G., C. Moos, and R. Starr. A new protein of the thick filaments of vertebrate skeletal myofibrils: extraction, purification and characterization. J. Mol. Biol. 74: 653–676, 1973.
 182. Olah, G. A., S. E. Rokop, C‐L. A. Wang, S. L. Blechner, and J. Trewhella. Troponin I encompasses an extended troponin C in the Ca2+‐bound complex: a small‐angle X‐ray and neutron scattering study. Biochemistry 33: 8233–8239, 1994.
 183. Palmiter, K. A., Y. Kitada, M. Muthuchamy, D. F. Wieczorek, and R. J. Solaro. Exchange of ã‐tropomyosin for α‐tropomyosin in hearts of transgenic mice induces changes in thin filament response to Ca2+, strong cross‐bridge binding, and protein phosphorylation. J. Biol. Chem. 271: 11611–11614, 1996.
 184. Palmiter, K. A., and R. J. Solaro. Molecular mechanisms regulating the myofilament response to Ca2+: implications of mutations causal for familial hypertrophic cardiomyopathy. Basic Res. Cardiol. 92 (Suppl 1): 63–74, 1997.
 185. Pan, B. S., A. M. Gordon, and Z. X. Luo. Removal of tropomyosin overlap modifies cooperative binding of myosin S‐1 to reconstituted thin filaments of rabbit striated muscle. J. Biol. Chem. 264: 8495–8498, 1989.
 186. Pan, B. S., A. M. Gordon, and J. D. Potter. Deletion of the first 45 NH2‐terminal residues of rabbit skeletal troponin T strengthens binding of troponin to immobilized tropomyosin. J. Biol. Chem. 266: 12432–12438, 1991.
 187. Pan, B. S., and R. J. Solaro. Calcium‐binding properties of troponin C in detergent‐skinned heart muscle fibers. J. Biol. Chem. 262: 7839–7849, 1987.
 188. Pan, B. S., K. A. Palmiter, M. Plonczynski, and R. J. Solaro. Slowly exchanging calcium binding sites unique to cardiac/slow muscle troponin C. J. Mol. Cell. Cardiol. 10: 1117–1124, 1990.
 189. Patel, J. R., G. M. Diffee, and R. L. Moss. Myosin regulatory light chain modulates the Ca2+ dependence of the kinetics of tension development in skeletal muscle fibers. Biophys. J. 70: 2333–2340, 1996.
 190. Patel, J. R., G. M. Diffee, X. P. Huang, and R. L. Moss. Phosphorylation of myosin regulatory light chain eliminates force‐dependent changes in relaxation rates in skeletal muscle. Biophys. J. 74: 360–368, 1998.
 191. Paul, K., N. A. Ball, G. W. Dorn II, and R. A. Walsh. Left ventricular stretch stimulates angionensin II‐mediated phosphati‐dylinositol hydrolysis and prtein kinase ɛ isoform translocation in adult guinea pig hearts. Circ. Res. 81: 643–650, 1997.
 192. Pearlstone, J. R., and L. B. Smillie. Binding of troponin T fragments to several types of tropomyosin. Sensitivity to Ca2+ in the presnece of troponin‐C. J. Biol. Chem. 257: 10587–10592, 1982.
 193. Pearlstone, J. R., and L. B. Smillie. Effects of troponin‐1 plus‐C on the binding of troponin‐T and its fragments to α‐tropomyosin. J. Biol. Chem. 258: 2534–2542, 1983.
 194. Pearlstone, J. R., and L. B. Smillie. Evidence for two‐site binding of troponin I inhibitory peptides to the N and C domains of troponin C. Biochemistry 34: 6932–6940, 1995.
 195. Persechini, A. and J. T. Stull. Phosphorylaton kinetics of skeletal muscle myosin and the effect of phosphorylation on actomyosin adenosinetriphosphatase activity. Biochemistry 23: 4144–4150, 1984.
 196. Persechini, A., J. T. Stull, and R. Cooke. The effect of myosin phosphorylation on the contractile properties of skinned rabbit skeletal muscle fibers. J. Biol. Chem. 260: 7951–7954, 1985.
 197. Phillips, G. N., Jr., J. P. Fillers, and C. Cohen. Tropomyosin crystal structure and muscled regulation. J. Mol. Biol. 192: 111–131, 1986.
 198. Potter, J. D., Z. Sheng, B.‐S. Pan, and J. Zhao. A direct regulatory role for troponin T and a dual role for troponin C in the Ca2+ regulation of muscle contraction. J. Biol. Chem. 270: 2557–2562, 1995.
 199. Pucéat, M., O. Clement, P. Lechene, J. M. Pelosin, R. Ventura‐Clapier, and G. Vassort. Neurohormonal control of calcium sensitivity of myofilaments in rat single heart cells. Circ. Res. 67: 517–524, 1990.
 200. Pucéat, M. and G. Vassort. Signaling by protein kinase C iso‐forms in the heart. Mol. Cell. Biochem. 157: 65–72. 1996.
 201. Rarick, H. M., H.‐P. Tang, X.‐D. Guo, A. F. Martin, and R. J. Solaro. Interactions at the NH2‐terminal interface of cardiac troponin I modulate myofilament activation. J. Mol. Cell. Cardiol. 31: 363–375, 1999.
 202. Rarick, H. M., X. Tu, R. J. Solaro, and A. M. Martin. The C‐terminus of cardiac troponin I is essential for full inhibitory activity and Ca2+‐sensitivity of rat myofibrils. J. Biol. Chem. 272: 26887–26892, 1997.
 203. Rarick, H. M., T. J. Opgenorth, T. W. von Geldern, and R. J. Solaro. An essential myosin light chain peptide stimulates cardiac myofibrillar ATPase activity. J. Biol. Chem. 271: 27039–27043, 1996.
 204. Rayment, I., W. R. Rypniewski, K. Schmidt‐Base, R. Smith, D. R. Tomchick, M. M. Benning, D. A. Winkelmann, G. Wesenberg, and H. M. Holden. Three‐dimensional structure of myosin subfragment‐1: a molecular motor. Science 261: 50–58, 1993.
 205. Rayment, I., H. M. Holden, M. Whittaker, C. B. Yohn, M. Lorenz, K. C. Holmes, and R. A. Milligan. Structure of the actinmyosin complex and its implications for muscle contraction. Science 261: 58–65, 1993.
 206. Reiffert, S. U., K. Jaquet, L. M. Fr. Heilmeyer, M. D. Ritchie, and M. A. Geeves. Bisphosphorylation of cardiac troponin I modulates the Ca(2+‐dependent binding of myosin fragment S1 to reconstituted thin filaments. FEBS Lett. 384: 43–47, 1996.
 207. Reiffert, S. U., K. Jaquet, L. M. Heilmeyer Jr., and F. W. Herberg. Stepwise subunit interaction changes by mono‐ and bisphosphorylation of cardiac troponin I. Biochemistry 37: 13516–13525, 1998.
 208. Risnik, V. V., and N. B. Gusev. Some properties of the nucleotide‐binding site of troponin T kinase‐casein kinase type II from skeletal muscle. Biochim. Biophys. Acta. 790: 108–116, 1984.
 209. Risnik, V. V., A. B. Dobrovolskii, N. B. Gusev, and S. E. Severin. Phosphorylase kinase phosphorylation of skeletal‐muscle troponin T. Biochem. J. 191: 851–854, 1980.
 210. Risnik, V. V., A. V. Vorotnikov, and N. B. Gusev. Phosphorylation of troponin T by Ca‐phospholipid‐dependent protein kinase. Biomed. Biochim. Acta 46: S444–S447, 1987.
 211. Robertson, S. P., J. D. Johnson, M. J. Holroyde, E. G. Kranias, J. D. Potter, R. J. Solaro. The effect of troponin I phosphorylation on the Ca2+‐binding properties of the Ca2+‐regulatory site of bovine cardiac troponin. J. Biol. Chem. 257: 260–263, 1982.
 212. Rossmanith, G. H., J. F. Hoh, L. Turnbull, R. I. Ludowyke. Mechanism of action of endothelin in rat cardiac muscle: crossbridge kinetics and myosin light chain phosphorylation. J. Physiol. (Lond.) 505: 217–227, 1997.
 213. Rüegg, J. C., C. Zeugner, J. Van Eyk, C. M. Kay, and R. S. Hodges. Inhibition of TnI‐TnC interaction and contraction of skinned muscle fibres by the synthetic peptide TnI [104–115]. Pflugers Arch. 414: 430–436, 1989.
 214. Saeki, Y., K. Shiozawa, K. Yanagisawa, and T. Shibata. Adrenaline increases the rate of cross‐bridge cycling in rat cardiac muscle. J. Mol. Cell. Cardiol. 22: 453–460, 1990.
 215. Sakata, Y., B. D. Hoit, S. B. Liggett, R. A. Walsh, and G. W. Dorn II. Decompensation of pressure‐overload hypertrophy in Gαq overexpressing mice. Circulation 97: 1488–1495, 1998.
 216. Sato, Y., D. G. Ferguson, H. Sako, G. W. Dorn II, V. J. Kadambi, A. Yatani, B. D. Hoit, R. A. Walsh, and E. G. Kranias. Cardiac‐specific overexpression of mouse cardiac calsequestrin is associated with depressed cardiovascular function and hypertrophy in transgenic mice. J. Biol. Chem. 273: 28470–28477, 1998.
 217. Sayers, S. T., and K. Bárány. Myosin light chain phosphorylation during contraction of turtle heart. FEBS Lett. 154: 305–310, 1983.
 218. Schaertl, S., S. S. Lehrer, and M. A. Geeves. Separation and characterization of the two functional regions of troponin T involved in muscle thin filament regulation. Biochemistry 34: 15890–15894, 1995.
 219. Schlender, K. K., T. J. Thysseril, and M. G. Hegazy. Calcium‐dependent phosphorylation of bovine cardiac C‐protein by phosphorylase kinase. Biochem. Biophys. Res. Commun. 155: 45–51, 1988.
 220. Schlender, K., and L. Bean. Phosphorylation of chicken cardiac C protein by calcium calmodulin‐dependent protein kinase II. Biol. Chem. 266: 2811–2817, 1991.
 221. Sham, J. S. K., L. R. Jones, and M. Morad. Phospholamban mediates the ã‐adrenergic‐enhanced Ca2+ uptake in mammalian ventricular myocytes. Am. J. Physiol. 261 (Heart Circ. Physiol. 30): H1344–H1349, 1991.
 222. Silver, P. J., L. M. Buja, and J. T. Stull. Frequency‐dependent myosin light chain phosphorylation in isolated myocardium. J. Mol. Cell. Cardiol. 18: 31–37, 1986.
 223. Solaro, R. J. Protein phosphorylation and the cardiac myofilaments. In: Protein Phosphorylation in Heart, edited by R. J. Solaro, Boca Raton, FL: CRC Press, 1986: 129–156.
 224. Solaro, R. J., and J. Van Eyk. Altered interactions among thin filament proteins modulate cardiac function. J. Mol. Cell. Cardiol. 28: 217–230, 1996.
 225. Solaro, R. J., A. J. G. Moir, S. V. Perry. Phosphorylation of troponin I and the inotropic effect of adrenalin in the perfused rabbit heart. Nature 262: 615–617, 1976.
 226. Solaro R. J. Heart failure and the response of cardiac myofilaments to Ca2+. Heart Failure 10: 150–155, 1994.
 227. Solaro, R. J., and H. M. Rarick. Troponin and tropomyosin: proteins that switch on and tune in the activity of cardiac myofilaments. Circ. Res. 83: 471–480, 1998.
 228. Solaro, R. J. Modulation of activation of cardiac myofilaments by beta‐adrenergic agonists. In: Modulation of Cardiac Calcium Sensitivity, edited by D. A. G. Allen, and J. A. Lee, Oxford. Oxford University Press 160–177, 1993.
 229. Spyracoupoulos, L., M. X. Li, S. K. Sia, S. M. Gagne, M. Chandra, R. J. Solaro, and B. D. Sykes. Calcium‐induced structural transition in the regulatory domain of human cardiac troponin C. Biochemistry 36: 12138–12146, 1997.
 230. Squire, J. M., J. J. Harford, and H. A. Al‐Khayat. Molecular movements in contracting muscle: towards “muscle—the movie”. Biophys. Chem. 50: 87–96, 1994.
 231. Squire, J. M., and E. P. Morris. A new look at thin filament regulaton in vertebrate skeletal muscle. FASEB J. 12: 761–771, 1998.
 232. Squire, J. M., H. A. Al‐Khayat, and N. Yagi. Muscle thin filament structure and regulation: actin subdomain movements and the tropomyosin shift modelled from low angle X‐ray diffraction. J. Chem. Soc. Faraday Trans. 89: 2717–2726, 1993.
 233. Starr, R. and G. Offer. The interaction of C‐protein with heavy meromyosin and subfragment‐2. Biochem. J. 171: 813–816, 1978.
 234. Stefancik, R., P. K. Jha, and S. Sarkar. Identification and mutagenesis of a highly conserved domain in troponin T responsible for troponin I binding: potential role for coiled‐coil interaction. Proc. Natl. Acad. Sci. U.S.A. 95: 957–962, 1998.
 235. Strang, K. T., and R. L. Moss. α1‐Adrenergic receptor stimulation decreases maximum shortening velocity of skinned single ventricular myoctyes from rats. Circ. Res. 77: 114–120, 1995.
 236. Strang, K. T., N. K. Sweitzer, M. L. Greaser, and R. L. Moss. ã‐Adrenergic receptor stimulation increases unloaded shortening velocity of skinned single ventricular myocytes from rats. Circ. Res. 74: 542–549, 1994.
 237. Strauss, J. D., J. E. Van Eyk, Z. Barth, L. Kluwe, R. J. Wiesner, K. Maeda, J. C. Ruegg. Recombinant troponin I substitution and calcium responsiveness in skinned cardiac muscle. Pflugers Arch. 431: 853–862, 1996.
 238. Stull, J. T., C. J. Sanford, D. R. Manning D. K. Blumenthal, and C. W. High. Phosphorylation of myofibrillar proteins in striated muscle,. Cold Spring Harbor Conf. Cell Prolif. 8: 823–891, 1981.
 239. Sugden, P. H., and A. Clerk. Cellular mechanisms of cardiac hypertrophy. J. Mol. Med. 76: 725–746, 1998.
 240. Swartz, D. R., and R. L. Moss. Influence of a strong binding myosin analog on calcium sensitive mechanical properties of skinned skeletal muslce fibers. J. Biol. Chem. 267: 20497–20506, 1992.
 241. Swiderek, K., K. Jaquet H. E. Meyer, C. Schachtele, F. Hofmann, and L. M. Heilmeyer Jr. Sites phosphorylated in bovine cardiac troponin T and I. Characterization by 31P‐NMR spectroscopy and phosphorylation by protein kinases. Eur. J. Biochem. 190: 575–582, 1990.
 242. Swiderek, K., K. Jaquet, H. E. Meyer, and M. G. Heilmeyer Jr. Cardiac troponin I, isolated from bovine heart, contains two adjacent phosphoserines. A first example of phosphoserine determination by derivatization to S‐ethylcysteine. Eur. J. Biochem. 176: 335–342, 1988.
 243. Syska, H., J. M. Wilkinson, R. J. A. Grand, and S. V. Perry. The relationship between biological activity and primary structure of troponin I from white skeletal muscle of the rabbit. Biochem. J. 153: 375–387, 1976.
 244. Szczesna, D., J. Zhao, and J. D. Potter. The regulatory light chains of myosin modulate cross‐bridge cycling in skeletal muscle. J. Biol. Chem. 271: 5246–5250, 1996.
 245. Takeishi, Y., G. Chu, D. M. Kirkpatrick, Z. Li, H. Wakasaki, E. G. Kranias, G. L. King, and R. A. Walsh. In vivo phosphorylation of cardiac troponin I by protein kinase C ã2 decreases cardiomyocyte calcium responsiveness and contractility in transgenic mouse hearts. J. Clin. Invest. 102: 72–78, 1998.
 246. Talbot, J. A., and R. S. Hodges. Synthetic studies on the inhibitory region of rabbit skeletal troponin I. J. Biol. Chem. 256: 2798–2802, 1981.
 247. Talosi, L., and E. G. Kranias. Effect of alpha‐adrenergic stimulation on activation of protein kinase C and phosphorylation of proteins in intact rabbit hearts. Circ. Res. 70: 670–678, 1992.
 248. Tanokura, M., Y. Tawada, A. Ono, and I. Ohtsuki. Chymotryptic subfragments on troponin T from rabbit skeletal muscle. Interactions with tropomyosin, troponin I and troponin C. J. Biochem. (Tokyo) 93: 331–337, 1983.
 249. Tao, T., B.‐J. Gong, and P. C. Leavis. Calcium‐induced movement of troponin‐I relative to actin in skeletal muscle thin filaments. Science 247: 1339–1341, 1990.
 250. Tawada, Y., H. Ohara, T. Ooi, and K. Tawada. Nonpolymerizable tropomyosin and control of the superprecipitation of actomyosin. J. Biochem. 78: 65–72, 1975.
 251. Terzic, A., M. Puceat, O. Clement, F. Scamps, and G. Vassort. α1‐Adrenergic effects on intracellular pH and calcium and on myofilaments in single rat cardiac cells. J. Physiol. (Lond.) 447: 275–292, 1992.
 252. Thierfelder, L., H. Watkins, C. MacRae, R. Lamas, W. Mc‐Kenna, H. P. Vosberg, J. G. Seidman, and C. E. Seidman. Alpha‐tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere. Cell 77: 701–712, 1994.
 253. Tobacman, L. S. Thin filament‐mediated regulation of cardiac contraction. Annu. Rev. Physiol. 58: 447–481, 1996.
 254. Tobacman L. S., and R. Lee. Isolation and functional comparison of bovine cardiac troponin T isoforms. J. Biol. Chem. 262: 4059–4064, 1987.
 255. Trautwein, W., and J. Hescheler. Regulation of cardiac L‐type calcium current by phosphorylation and G proteins. Annu. Rev. Physiol. 52: 257–274, 1990.
 256. Tripet, B., J. E. Van Eyk, and R. S. Hodges. Mapping of a second actin‐tropomyosin and a second troponin C binding site within the C terminus of troponin I, and their importance in the Ca2+‐dependent regulation of muscle contraction. J. Mol. Biol. 271: 728–750, 1997.
 257. Ueno, H. Local structural changes in tropomyosin detected by a trypsin‐probe method. Biochemistry 23: 4791–4798, 1984.
 258. Van Eyk, J. E., and R. S. Hodges. The use of synthetic peptides to unravel the mechanism of muscle regulation. Methods: A Companion to Methods in Enzymology. 5: 264–280, 1993.
 259. Van Eyk, J. E., and R. S. Hodges. The biological importance of each amino acid residue of the troponin I inhibitory sequence 104–115 in the interaction with troponin C and tropomyosin–actin. J. Biol. Chem. 263: 1726–1732, 1988.
 260. Van Eyk, J. E., C. M. Kay, and R. S. Hodges. A comparative study of the interactions of synthetic peptides of the skeletal and cardiac troponin I inhibitory region with skeletal and cardiac troponin C. Biochemistry 30: 9974–9981, 1991.
 261. Vassylyev, D. G., S. Takeda, S. Wakatsuki, K. Maeda, and Y. Maeda. The crystal structure of troponin C in complex with N‐terminal fragment of troponin I. The mechanism of how the inhibitory action of troponin I is released by Ca(2+)‐binding to troponin C. Adv. Exp. Med. Biol. 453: 157–167, 1998.
 262. Venema, R. C., and J. F. Kuo. Protein kinase C‐mediated phosphorylation of troponin I and C‐protein in isolated myocardial cells is associated with inhibition of myofibrillar actomyosin ATPase. J. Biol. Chem. 268: 2705–2711, 1993.
 263. Venema, R. C., R. L. Raynor, T. A. Noland, and J. F. Kuo. Role of protein kinase C in the phosphorylation of cardiac myosin light chain 2. Biochem. J. 294: 401–406, 1993.
 264. Villar‐Palasi, C. and A. Kumon. Purification and properties of dog cardiac troponin T kinase. J. Biol. Chem. 256: 7409–7415, 1981.
 265. Wang, Z. Y., S. Sarkar, J. Gergely, and T. Tao. Ca2(+)‐dependent interactions between the C‐helix of troponin‐C and troponin‐I. Photocross‐linking and fluorescence studies using a recombinant troponin‐C. J. Biol. Chem. 265: 4953–4957, 1990.
 266. Watkins, H., D. Conner, L. Thierfelder, J. A. Jarcho, C. MacRae, W. J. McKenna, B. J. Maron, J. G. Seidman, and C. E. Seidman. Mutations in the cardiac myosin binding protein‐C gene on chromosome 11 cause familial hypertrophic cardiomyopathy. Nat. Genet. 11: 434–437, 1995.
 267. Watkins, H., W. J. McKenna, L. Thierfelder, H. J. Suk, R. Anan, A. O'Donoghue, P. Spirito, A. Matsumori, C. S. Moravec, J. G. Seidman, and C. E. Seidman. Mutations in the genes for cardiac troponin T and α‐tropomyosin in hypertrophic cardiomyopathy. N. Engl. J. Med. 332: 1058–1064, 1995.
 268. Wattanapermpool, J., X. Guo, and R. J. Solaro. The unique amino‐terminal peptide of cardiac troponin I regulates myofibrillar ATPase activity only when it is phosphorylated. J. Mol. Cell. Cardiol. 27: 1383–1391, 1995.
 269. Weisberg, A. and S. Winegrad. Alteration of myosin cross bridges by phosphorylation of myosin‐binding protein C in cardiac muscle. Proc. Natl. Acad. Sci. U.S.A. 93: 8999–9003, 1996.
 270. Weisberg, A., and S. Winegrad. Relation between crossbridge structure and actomyosin ATPase activity in rat heart. Circ. Res. 83: 60–72, 1998.
 271. Westwood, S. A., and S. V. Perry. The effect of adrenaline on the phosphorylation of the P light chain of myosin and troponin‐I in the perfused rabbit heart. Biochem. J. 197: 185–193, 1981.
 272. White, S. P., C. Cohen, and J. G. N. Phillips. Structure of cocrystals of tropomyosin and troponin. Nature 325: 826–828, 1987.
 273. Wilkinson, J. M., and R. J. A. Grand. Comparison of amino acid sequence of troponin I from different striated muscles. Nature 271: 31–35, 1978.
 274. Williams, D. L., Jr., L. E. Greene, and E. Eisenberg. Cooperative turning on of myosin subfragment 1 adenosinetriphosphatase activity by the troponin‐tropomyosin‐actin complex. Biochemistry 27: 6987–6993, 1988.
 275. Wolff, M. R., S. H. Buck, S. W. Stoker, M. L. Greaser, and R. M. Mentzer. Myofibrillar calcium sensitivity of isometric tension is increased in human dilated cardiomyopathies: role of altered beta‐adrenergically mediated protein phosphorylation. J. Clin. Invest. 98: 167–176, 1996.
 276. Wolska, B. M., M. O. Stojanovic, W. Luo, E. G. Kranias, and R. J. Solaro. Effect of ablation of phospholamban on dynamics of cardiac myocyte contraction and intracellular Ca2+. Am. J. Physiol. 271 (Cell Physiol. 40): C391, 1996.
 277. Wolska, B. M., R. S. Keller, C. C. Evans, K. A. Palmiter, R. M. Phillips, M. Muthuchamy, J. Oehlenschlager, D. F. Wieczorek, P. P. de Tombe, and R. J. Solaro. Correlation between myofilament response to Ca2+ and altered dynamics of contraction and relaxation in transgenic cardiac cells expressing ã‐tropomyosin. Circ. Res. 84: 745–751, 1999.
 278. Yang, Z., J. T. Stull, R. J. Levine, and H. L. Sweeney. Changes in interfilament spacing mimic the effects of myosin regulatory light chain phosphorylation in rabbit psoas fibers. J. Struct. Biol. 122: 139–148, 1998.
 279. Zhang, R., J. Zhao, A. Mandveno, and J. D. Potter. Cardiac troponin I phosphorylation increases the rate of cardiac muscle relaxation. Circ. Res. 76: 1028–1035, 1995.
 280. Zhang R., J.‐J. Zhao, and J. D. Potter. Phosphorylation of both serine residues in cardiac troponin I is required to decrease the Ca2+ affinity of cardiac troponin C. J. Biol. Chem. 270: 30773–30780, 1995.
 281. Zhou, X., E. P. Morris, S. S. Lehrer. Binding of troponin I and the troponin I‐troponin C complex to actin‐tropomyosin. Dissociation by myosin subfragment 1. Biochemistry 39: 1128–1132, 2000.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite

R. John Solaro. Modulation of Cardiac Myofilament Activity by Protein Phosphorylation. Compr Physiol 2011, Supplement 6: Handbook of Physiology, The Cardiovascular System, The Heart: 264-300. First published in print 2002. doi: 10.1002/cphy.cp020107