Myosin Binding Protein-C Slow is a Novel Substrate for Protein Kinase A (PKA) and C (PKC) in Skeletal Muscle
Myosin Binding Protein-C Slow is a Novel Substrate for Protein Kinase A (PKA) and C (PKC) in Skeletal Muscle
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DOI：
10.1021/pr200355w
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发表时间：
2011-10-01
影响因子：
4.4
通讯作者：
Kontrogianni-Konstantopoulos, Aikaterini
中科院分区：
文献类型：
--
作者：
Ackermann, Maegen A.;Kontrogianni-Konstantopoulos, Aikaterini
肌球蛋白结合蛋白-C慢（MyBP-C慢），一个家族的厚毒力相关蛋白，由四个可变剪接形式，即变体1-4。变体1-4具有共同的结构和序列;然而，它们在三个区域中不同：变体1和2在NH（2）末端含有一个新的25个残基长插入，变体3在免疫球蛋白（IG）结构域C7内携带一个18个氨基酸长的片段，而变体1含有一个独特的由26个氨基酸组成的COOH末端，而变体4不具有任何这些插入。变体1-4在骨骼肌中以可变的量表达，表现出不同的形貌和潜在的不同功能。迄今为止，调节MyBP-C慢活性的调节机制尚不清楚。使用一系列的蛋白质组学方法，我们表明，MyBP-C慢包括一个家庭的磷蛋白。Ser-59和Ser-62是PKA的底物，而Ser-83和Thr-84是PKC的底物。此外，Ser-204是两种PICA的底物。和PKC。重要的是，磷酸化骨骼MyBP-C蛋白（即，慢和快）在小鼠营养不良肌肉中显著增加，即使它们的总量显著降低。简而言之，我们的研究首次表明MyBP-C慢亚家族经历磷酸化，这可能调节其在正常和疾病中的活动。
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 PICA. 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.