cAMP-dependent protein kinase: a framework for a diverse family of enzymes.
cAMP-dependent protein kinase: a framework for a diverse family of enzymes.
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cAMP 依赖性蛋白激酶：多种酶家族的框架。
DOI：
10.1101/sqb.1988.053.01.018
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Dospmann,W
中科院分区：
文献类型：
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作者：
Taylor,SS;Buechler,JA;Slice,LW;Knighton,DK;Durgerian,S;Ringheim,GE;Neitzel,JJ;Yonemoto,WM;Sowadski,JM;Dospmann,W
最早被发现的蛋白激酶之一是响应cAMP而被激活的酶，cAMP依赖性蛋白激酶（Walsh et al. 1968）。在这期间的几十年里，已经发现了许多不同的激酶（Hanks et al. 1988）。它们包括将磷酸盐转化为丝氨酸和苏氨酸的激酶以及将磷酸盐转化为酪氨酸的激酶。一些激酶被第二信使激活，如cAMP、Ca - t~和二酰基甘油，而另一些则被主要信号激活，如生长因子。蛋白激酶家族包括由癌基因和生长因子受体编码的转化蛋白（回顾，见Boyer和Krebs 1986）。在许多方面，camp依赖性蛋白激酶是整个激酶家族的原型；然而，它的激活机制是不寻常的，也许是唯一的蛋白激酶。在缺乏cAMP的情况下，该酶是一种非活性四聚体，含有两个调节亚基(R)和两个催化亚基(C)。除了转化的致癌激酶外，蛋白激酶是典型的严格调控酶，在缺乏激活配体的情况下保持非活性形式，当细胞内cAMP水平升高时，cAMP依赖性蛋白激酶被激活。真核细胞中cAMP的主要受体是cAMP依赖性蛋白激酶的调控亚基。cAMP的结合诱导调控亚基的构象变化，稳定对催化亚基亲和力较低的结构，从而促进酶复合物的解离。解离催化亚基（M r= 38,900）具有催化活性，其在调节许多底物蛋白活性方面的调节作用已被充分记录（Krebs and Beavo 1979; Bramson et al. 1984）。尽管整个蛋白激酶家族中存在多样性，但许多结构和功能特征是共享的。特别是，每个蛋白激酶都有一个保守的催化核心，这表明这些酶在一定程度上是从一个共同的起源进化而来的。在这方面，camp依赖性蛋白激酶不仅是最小的蛋白激酶之一，也是最简单的蛋白激酶之一，因为主要的调控元件是一个容易解离的独特亚基的一部分。剩余的催化亚基与每个激酶的催化区域和残基具有广泛的序列相似性
One of the first protein kinases to be discovered was the enzyme that is activated in response to cAMP, cAMP-dependent protein kinase (Walsh et al. 1968). In the intervening decades, many diverse kinases have been identified (Hanks et al. 1988). They include kinases that transfer phosphate to serine and threonine as well as those transferring phosphate to tyrosine. Some kinases are activated in response to second messengers, such as cAMP, Ca t~, and diacylglycerol, whereas others are activated by primary signals such as growth factors. The protein kinase family includes transforming proteins coded by oncogenes as well as growth factor receptors (for reviews, see Boyer and Krebs 1986).In many ways, cAMP-dependent protein kinase serves as a prototype for the entire kinase family; however, its mechanism of activation is unusual and perhaps unique among the protein kinases. In the absence of cAMP, the enzyme is an inactive tetramer containing two regulatory (R) and two catalytic (C) subunits. With the exception of the transforming oncogenic kinases, the protein kinases are characteristically tightly regulated enzymes and are maintained in an inactive form in the absence of activating ligands, cAMP-dependent protein kinase is activated when intracellular cAMP levels are elevated. The major receptor for cAMP in eukaryotic cells is the regulatory subunit of cAMP-dependent protein kinase. Binding of cAMP induces conformational changes in the regulatory subunit that stabilize a structure having a lowered affinity for the catalytic subunit, thus promoting dissociation of the hoioenzyme complex. The dissociated catalytic subunit (M r= 38,900) is catalytically active, and its regulatory role in modulating the activity of many substrate proteins has been well documented (Krebs and Beavo 1979; Bramson et al. 1984). Despite the diversity seen in the overall protein kinase family, many features of structure and function are shared. In particular, each protein kinase has a conserved catalytic core, indicating that these enzymes have evolved in part from a common origin. In this regard, cAMP-dependent protein kinase is not only one of the smallest protein kinases, but also one of the simplest, for the major regulatory elements are part of a distinct subunit that easily dissociates. The remaining catalytic subunit shares extensive sequence similarities with the catalytic region of every kinase, and residues