Substrate and Docking Interactions in Serine/Threonine Protein Kinases
Substrate and Docking Interactions in Serine/Threonine Protein Kinases
复制标题
DOI：
10.1002/chin.200805268
复制
发表时间：
2008-01
期刊：
影响因子：
--
通讯作者：
E. Goldsmith;Radha Akella;Xiaoshan Min;Tianjun Zhou;J. Humphreys
中科院分区：
文献类型：
--
作者：
E. Goldsmith;Radha Akella;Xiaoshan Min;Tianjun Zhou;J. Humphreys
Protein kinases have emerged as the largest family of signaling proteins in eukaryotic cells and are involved in every aspect of cellular regulation. There are over 500 protein kinases in the human genome. 1, 2 The vast majority are Ser/Thr protein kinases. The Ser/Thr protein kinases interact with diverse substrates ranging from enzymes, including other kinases, to transcription factors, receptors, and other regulatory proteins. Thus, mechanisms to ensure specificity must be present. However, from emerging structural data it is becoming apparent that the ways in which protein kinases interact with their substrates local to the active site are relatively few. Instead, docking interactions, in pockets or grooves outside the active site of the kinase, are used to recognize substrates and other interacting proteins. Docking motifs in substrates bind in docking grooves within the kinase domain or adaptor protein. Docking interactions have been defined for CDKs (cyclin-dependent kinases), MAPKs (mitogen-activated protein kinases), and members of the AGC group (cAMP-dependent (PKA), cGMP-dependent (PKC)), as well as several other kinases. Further, structural data is revealing that docking interactions regulate kinase activity by unanticipated allosteric mechanisms that probably promote pathway specificity.In this review, we outline the current structural data available on distinct Ser/Thr protein kinases. How kinases bind substrates at the active site is described, focusing on the P+ 1 pocket, which is remodeled in inactive forms of several protein kinases. Substrate docking interactions, outside the active site, observed in MAP kinases, CDKs, and AGC kinases will be described. How specificity among these different families of kinases is achieved from the organization of the binding site and other factors will be discussed. Further, available data suggesting that docking interactions control kinase activity allosterically will be reviewed. Recent reviews of topics under discussion3-10 and related topics11-17 are available.
