Ca2+/S100 regulation of giant protein kinases
Ca2+/S100 regulation of giant protein kinases
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DOI：
10.1038/380636a0
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发表时间：
1996-04-18
期刊：
影响因子：
64.8
通讯作者：
Kemp, BE
中科院分区：
文献类型：
--
作者：
Heierhorst, J;Kobe, B;Kemp, BE
蛋白激酶的蛋白磷酸化在细胞过程中发挥着核心调节作用，并且这些激酶本身受到严格调节(1)。一种常见的调节机制涉及 Ca2+ 结合蛋白 (CaBP)，例如钙调蛋白 (CaM)(2)。在这里，我们通过证明 Ca2+/S100A1 对肌球蛋白相关巨蛋白激酶抽搐的特异性和 >1,000 倍的激活，报告了蛋白激酶激活的 Ca2+ 效应器机制(2)。 S100A1(2) 是 CaBP 大家族的成员，该家族参与多种细胞过程，包括细胞生长、分化和运动，但其分子作用很大程度上未知(3)。 S100A1(2) 结合位点是位于活性位点的自动调节序列的一部分，负责 twitchin 激酶的空间内自动抑制；基于两个 twitchin 激酶片段晶体结构的自抑制机制在别处有所描述 (4)。 Ca2+/S100 可能是涉及肌肉收缩和细胞骨架结构的整个巨型蛋白激酶家族的生理激活剂(2,5-9)。
Protein phosphorylation by protein kinases plays a central regulatory role in cellular processes and these kinases are themselves tightly regulated(1). One common mechanism of regulation involves Ca2+-binding proteins (CaBP) such as calmodulin (CaM)(2). Here we report a Ca2+-effector mechanism for protein kinase activation by demonstrating the specific and >1,000-fold activation of the myosin-associated giant protein kinase twitchin by Ca2+/S100A1(2). S100A1(2) is a member of a large CaBP family that is implicated in various cellular processes, including cell growth, differentiation and motility, but whose molecular actions are largely unknown(3). The S100A1(2)-binding site is a part of the autoregulatory sequence positioned in the active site that is responsible for intrasteric autoinhibition of twitchin kinase; the mechanism of autoinhibition based on the crystal structures of two twitchin kinase fragments is described elsewhere(4). Ca2+/S100 represents a likely physiological activator for the entire family of giant protein kinases involved in muscle contractions and cytoskeletal structure(2,5-9).