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PMID: 7744002 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Phosphorylation switches specific for the cardiac isoform of myosin binding protein-C: a modulator of cardiac contraction?

The EMBO journal ·Vol. 14 ·No. 9 ·1995-05-01 ·Pages 1952-60

Gautel M, Zuffardi O, Freiburg A, Labeit S

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.

MeSH Terms
Amino Acid Sequence Animals Binding Sites Cardiomyopathy, Hypertrophic/genetics Carrier Proteins/genetics,isolation & purification,metabolism Chickens Chromosome Mapping Chromosomes, Human, Pair 11 Cloning, Molecular Genetic Linkage Humans In Situ Hybridization, Fluorescence In Vitro Techniques Molecular Sequence Data Myocardial Contraction/physiology Myocardium/metabolism Myosins/metabolism Phosphorylation Rabbits Sequence Homology, Amino Acid
Chemicals
Carrier Proteins myosin-binding protein C Myosins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Gautel M
European Molecular Biology Laboratory, Heidelberg, Germany.
Zuffardi O
Freiburg A
Labeit S
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1995-05-01
Pages
1952-60
Language
English
Region
England
NLM ID
8208664
PMCID
PMC398294
Subset
IM
Databases
GENBANK
X84075
External Links
PubMed source PMC Full Text View journal details
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