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

摘要: Cardiac myosin binding protein-C (cardiac MyBP-C, cardiac C protein) belongs to a family of proteins implicated in both regulatory and structural functions striated muscle. For the isoform, phosphorylation vivo by cAMP-dependent protein kinase (PKA) upon adrenergic stimulation is linked modulation contraction. The sequence human MyBP-C now reveals motifs specific for this isoform. Site-directed mutagenesis identifies LAGGGRRIS loop N-terminal region as key substrate site PKA calmodulin-dependent associated with native protein. Phosphorylation two further sites induced isoform-specific site. This switch can be mimicked aspartic acid instead phosphoserine. therefore specifically equipped sensors regulation contraction, possibly implicating disease. gene coding has been assigned chromosomal location 11p11.2 humans, physical linkage subsets familial hypertrophic cardiomyopathy (FHC). makes candidate chromosome 11-associated FHC.