title: Myosin binding protein-C slow is a novel substrate for protein kinase A (PKA) and C (PKC) in skeletal muscle.
abstract: Myosin Binding Protein-C slow (MyBP-C slow), a family of thick filament-associated proteins, consists of four alternatively spliced forms, namely variants 1-4. Variants 1-4 share common structures and sequences; however, they differ in three regions: variants 1 and 2 contain a novel 25-residue long insertion at the extreme NH(2)-terminus, variant 3 carries an 18-amino acid long segment within immunoglobulin (Ig) domain C7, and variant 1 contains a unique COOH-terminus consisting of 26-amino acids, while variant 4 does not possess any of these insertions. Variants 1-4 are expressed in variable amounts among skeletal muscles, exhibiting different topographies and potentially distinct functions. To date, the regulatory mechanisms that modulate the activities of MyBP-C slow are unknown. Using an array of proteomic approaches, we show that MyBP-C slow comprises a family of phosphoproteins. Ser-59 and Ser-62 are substrates for PKA, while Ser-83 and Thr-84 are substrates for PKC. Moreover, Ser-204 is a substrate for both PKA and PKC. Importantly, the levels of phosphorylated skeletal MyBP-C proteins (i.e., slow and fast) are notably increased in mouse dystrophic muscles, even though their overall amounts are significantly decreased. In brief, our studies are the first to show that the MyBP-C slow subfamily undergoes phosphorylation, which may regulate its activities in normalcy and disease.
authors: University of Maryland , School of Medicine, Department of Biochemistry and Molecular Biology, 108 North Greene Street, Baltimore, Maryland 21201, United States.
authors: Maegen A
authors: MA
authors: Ackermann
authors: Aikaterini
authors: A
authors: Kontrogianni-Konstantopoulos
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000378:metabolism*; D010748:Phosphopeptides / Q000737:chemistry; D010766:Phosphorylation; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012694:Serine / Q000737:chemistry; D013912:Threonine / Q000737:chemistry; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D010748:Phosphopeptides; D020033:Protein Isoforms; D011493:Protein Kinase C; D012694:Serine; D013912:Threonine; D000099163:Myosin Binding Protein C