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| PHOSPHORYLATION SWITCHES SPECIFIC FOR THE CARDIAC ISOFORM OF MYOSIN BINDING PROTEIN-C - A MODULATOR OF CARDIAC CONTRACTION |
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| Author(s): GAUTEL M, ZUFFARDI O, FREIBURG A, LABEIT S |
| Source: EMBO JOURNAL Volume: 14 Issue: 9 Pages: 1952-1960 Published: MAY 1 1995 |
| Times Cited: 154 References: 56 |
| Abstract: Cardiac myosin binding protein-C (cardiac MYBP-C, cardiac C protein) belongs to a family of proteins implicated in both regulatory and structural functions of striated muscle. For the cardiac isoform, regulatory phosphorylation in vivo by cAMP-dependent protein kinase (PKA) upon adrenergic stimulation is linked to modulation of cardiac contraction. The sequence of human cardiac MyBP-C now reveals regulatory motifs specific for this isoform. Site-directed mutagenesis identifies a LAGGGRRIS loop in the N-terminal region of cardiac MyBP-C as the key substrate site for phosphorylation by both PKA and a calmodulin-dependent protein kinase associated with the native protein. Phosphorylation of two further sites by PKA is induced by phosphorylation of this isoform-specific site. This phosphorylation switch can be mimicked by aspartic acid instead of phosphoserine. Cardiac MyBP-C is therefore specifically equipped with sensors for adrenergic regulation of cardiac contraction, possibly implicating cardiac MyBP-C in cardiac disease. The gene coding for cardiac MYBP-C has been assigned to the chromosomal location 11p11.2 in humans, and is therefore in a region of physical linkage to subsets of familial hypertrophic cardiomyopathy (FHC). This makes cardiac MyBP-C a candidate gene for chromosome 11-associated FHC. |
| Document Type: Article |
| Language: English |
| Reprint Address: GAUTEL, M (reprint author), EUROPEAN MOLEC BIOL LAB, MEYERHOFSTR 1, D-69117 HEIDELBERG, GERMANY |
Addresses:
1. UNIV PAVIA, PAVIA, ITALY |
| Publisher: OXFORD UNIV PRESS UNITED KINGDOM, WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: QX744 |
| ISSN: 0261-4189 |
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