Department of Pharmacology, University of California, San Diego, La Jolla, 92093-90654, USA.
Nat Rev Mol Cell Biol. 2012 Oct;13(10):646-58. doi: 10.1038/nrm3432. Epub 2012 Sep 20.
Protein kinases are dynamic molecular switches that have evolved to be only transiently activated. Kinase activity is embedded within a conserved kinase core, which is typically regulated by associated domains, linkers and interacting proteins. Moreover, protein kinases are often tethered to large macromolecular complexes to provide tighter spatiotemporal control. Thus, structural characterization of kinase domains alone is insufficient to explain protein kinase function and regulation in vivo. Recent progress in structural characterization of cyclic AMP-dependent protein kinase (PKA) exemplifies how our knowledge of kinase signalling has evolved by shifting the focus of structural studies from single kinase subunits to macromolecular complexes.
蛋白激酶是动态的分子开关，其进化为仅瞬时激活。激酶活性嵌入在保守的激酶核心中，该核心通常通过相关结构域、连接子和相互作用蛋白来调节。此外，蛋白激酶通常与大型大分子复合物结合，以提供更严格的时空控制。因此，激酶结构域的结构特征本身不足以解释蛋白激酶在体内的功能和调节。最近在环腺苷酸依赖性蛋白激酶 (PKA) 的结构特征方面的进展为例说明了我们对激酶信号的认识是如何通过将结构研究的重点从单个激酶亚基转移到大分子复合物来发展的。
