Phosphorylation of Ryanodine Receptors
Phosphorylation of Ryanodine Receptors
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DOI：
10.4067/s0716-97602004000400005
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发表时间：
2004-01-01
影响因子：
6.7
通讯作者：
HAMILTON, SUSAN L
中科院分区：
文献类型：
--
作者：
DANILA, CRISTINA I;HAMILTON, SUSAN L
心肌和骨骼肌兰尼碱受体（RyR）都是包括许多激酶和磷酸酶的大复合体的一部分。这些RyR在其胞质结构域中有几个潜在的磷酸化位点，但磷酸化的功能后果和负责的酶的身份一直是相当大的争议的主题。RYR 2（心脏亚型）中Ser-2809和RyR 1（骨骼亚型）中Ser-2843的过度磷酸化被认为会导致FK 506结合蛋白（FKBP）从RyR中解离，产生“渗漏通道”，但一些实验室发现磷酸化与FKBP结合之间没有关系。也有争议的是磷酸化这些丝氨酸的激酶的身份：cAMP依赖性蛋白激酶（PKA）与钙调蛋白激酶II（CaMKII）。这些激酶的其他靶点的磷酸化也可以改变钙的全稳态。例如，PKA也磷酸化受磷蛋白（PLB），改变肌质内质网Ca 2 + ATP酶（SERCA）活性。本文综述了与RyRs磷酸化相关的主要发现和争议。
Both cardiac and skeletal muscle ryanodine receptors (RyRs) are parts of large complexes that include a number of kinases and phosphatases. These RyRs have several potential phosphorylation sites in their cytoplasmic domains, but the functional consequences of phosphorylation and the identity of the enzymes responsible have been subjects of considerable controversy. Hyperphosphorylation of Ser-2809 in RYR2 (cardiac isoform) and Ser-2843 in RyR1 (skeletal isoform) has been suggested to cause the dissociation of the FK506-binding protein (FKBP) from RyRs, producing "leaky channels," but some laboratories find no relationship between phosphorylation and FKBP binding. Also debated is the identity of the kinases that phosphorylate these serines: cAMP-dependent protein kinase (PKA) versus calmodulin kinase II (CaMKII). Phosphorylation of other targets of these kinases could also alter calcium holueostasis. For example, PKA also phosphorylates phospholamban (PLB), altering the Sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) activity. This review summarizes the major findings and controversies associated with phosphorylation of RyRs.