During the past 5 years there has been an increasing body of literature describing the roles cardiac myosin binding protein C (cMyBP-C) phosphorylation play in regulating cardiac function and heart failure. cMyBP-C is a sarcomeric thick filament protein that interacts with titin, myosin and actin to regulate sarcomeric assembly, structure and function. Elucidating the function of cMyBP-C is clinically important because mutations in this protein have been linked to cardiomyopathy in more than sixty million people worldwide. One function of cMyBP-C is to regulate cross-bridge formation through dynamic phosphorylation by protein kinase A, protein kinase C and Ca(2+)-calmodulin-activated kinase II, suggesting that cMyBP-C phosphorylation serves as a highly coordinated point of contractile regulation. Moreover, dephosphorylation of cMyBP-C, which accelerates its degradation, has been shown to associate with the development of heart failure in mouse models and in humans. Strikingly, cMyBP-C phosphorylation presents a potential target for therapeutic development as protection against ischemic-reperfusion injury, which has been demonstrated in mouse hearts. Also, emerging evidence suggests that cMyBP-C has the potential to be used as a biomarker for diagnosing myocardial infarction. Although many aspects of cMyBP-C phosphorylation and function remain poorly understood, cMyBP-C and its phosphorylation states have significant promise as a target for therapy and for providing a better understanding of the mechanics of heart function during health and disease. In this review we discuss the most recent findings with respect to cMyBP-C phosphorylation and function and determine potential future directions to better understand the functional role of cMyBP-C and phosphorylation in sarcomeric structure, myocardial contractility and cardioprotection.

中文翻译：

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心脏肌球蛋白结合蛋白-C 在健康和疾病中的磷酸化和功能。

在过去的 5 年中，越来越多的文献描述了心脏肌球蛋白结合蛋白 C (cMyBP-C) 磷酸化在调节心脏功能和心力衰竭中的作用。cMyBP-C 是一种肌节粗丝蛋白，可与肌动蛋白、肌球蛋白和肌动蛋白相互作用以调节肌节组装、结构和功能。阐明 cMyBP-C 的功能在临床上很重要，因为这种蛋白质的突变与全世界超过六千万人的心肌病有关。cMyBP-C 的一个功能是通过蛋白激酶 A、蛋白激酶 C 和 Ca(2+)-钙调蛋白活化激酶 II 的动态磷酸化来调节交叉桥的形成，这表明 cMyBP-C 磷酸化是一个高度协调的点。收缩调节。此外，cMyBP-C 的去磷酸化，加速其降解，已被证明与小鼠模型和人类心力衰竭的发展有关。引人注目的是，cMyBP-C 磷酸化为治疗开发提供了一个潜在的靶点，作为对缺血再灌注损伤的保护，这已在小鼠心脏中得到证实。此外，新出现的证据表明，cMyBP-C 有可能用作诊断心肌梗塞的生物标志物。尽管 cMyBP-C 磷酸化和功能的许多方面仍然知之甚少，但 cMyBP-C 及其磷酸化状态作为治疗靶点和提供对健康和疾病期间心脏功能机制的更好理解具有重要前景。