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Titolo:
CAPK-phosphorylation controls the interaction of the regulatory domain of cardiac myosin binding protein C with myosin-S2 in an on-off fashion
Autore:
Gruen, M; Prinz, H; Gautel, M;
Indirizzi:
Max Planck Inst Mol Physiol, Phys Biochem Abt, D-44227 Dortmund, Germany Max Planck Inst Mol Physiol Dortmund Germany D-44227 7 Dortmund, Germany
Titolo Testata:
FEBS LETTERS
fascicolo: 3, volume: 453, anno: 1999,
pagine: 254 - 259
SICI:
0014-5793(19990625)453:3<254:CCTIOT>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; KINASE-C; MYOFIBRILLAR PROTEIN; SKELETAL-MUSCLE; RABBIT HEARTS; TROPONIN-I; RAT-HEART; IDENTIFICATION; PHOSPHOLAMBAN; ISOFORM;
Keywords:
myosin binding protein C; myosin regulation; protein interaction; phosphorylation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Gautel, M European Mol Biol Lab, Struct Biol Div, Postfach 10 22 09, D-69012 Heidelberg, Germany European Mol Biol Lab Postfach 10 22 09 Heidelberg Germany D-69012
Citazione:
M. Gruen et al., "CAPK-phosphorylation controls the interaction of the regulatory domain of cardiac myosin binding protein C with myosin-S2 in an on-off fashion", FEBS LETTER, 453(3), 1999, pp. 254-259

Abstract

Myosin binding protein C is a protein of the myosin filaments of striated muscle which is expressed in isoforms specific for cardiac and skeletal muscle. The cardiac isoform is phosphorylated rapidly upon adrenergic stimulation of myocardium by cAMP-dependent protein kinase, and together with the phosphorylation of troponin-I and phospholamban contributes to the positive inotropy that results from adrenergic stimulation of the heart, Cardiac myosin binding protein C is phosphorylated by cAMP-dependent protein kinase onthree sites in a myosin binding protein C specific N-terminal domain whichbinds to myosin-S2. This interaction with myosin close to the motor domainis likely to mediate the regulatory function of the protein. Cardiac myosin binding protein C is a common target gene of familial hypertrophic cardiomyopathy and most mutations encode N-terminal subfragments of myosin binding protein C. The understanding of the signalling interactions of the N-terminal region is therefore important for understanding the pathophysiology ofmyosin binding protein C associated cardiomyopathy. We demonstrate here bycosedimentation assays and isothermal titration calorimetry that the myosin-S2 binding properties of the myosin binding protein C motif are abolishedby cAMP-dependent protein kinase-mediated trisphosphorylation, decreasing the S2 affinity from a K-d of approximate to 5 mu M to undetectable levels. We show that the slow and fast skeletal muscle isoforms are no cAMP-dependent protein kinase substrates and that the S2 interaction of these myosin binding protein C isoforms is therefore constitutively on, The regulation ofcardiac contractility by myosin binding protein C therefore appears to be a 'brake-off mechanism that will free a specific subset of myosin heads from sterical constraints imposed by the binding to the myosin binding proteinC motif. (C) 1999 Federation of European Biochemical Societies.

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Documento generato il 04/12/20 alle ore 22:20:22