丝裂原活化蛋白激酶(MAPK)生物学功能的结构基础

The Structural Basis of Biological Function of Mitogen-activated Protein Kinases

丝裂原活化蛋白激酶 (MAPK)是生物体内重要的信号转导系统之一 ,能对广泛的细胞外刺激发生反应 .蛋白激酶的空间构象是其功能的重要决定因素 .对MAPK蛋白结构的研究表明 ,MAPK的结构与功能之间具有密切的关系 .尽管MAPK各亚族的结构非常相似 ,但也存在着一些差异 ,这些差异是不同亚族对不同的细胞外刺激产生特异性反应的结构基础 .某些关键性结构 ,例如Loop12 ,在MAPK对上游激酶的作用、下游底物的选择以及亚细胞定位中都具有重要作用 .进一步深入研究MAPK的空间结构 ,探讨MAPK的生物学功能与其空间构象之间的关系 。

As key components of signal transduction systems in organisms, mitogen activated protein kinases (MAPKs) are considered to be involved in many cellular processes and pathogenesis of many severe diseases. So far, four subfamilies of MAPKs, i.e., ERK, JNK/SAPK, p38/RK and ERK5/BMK1, have been identified and cloned into mammalian cells. The conformational structure of a protein kinase is an important determinant of its function. The studies on the conformations of MAPKs showed that the structure and function of these signaling molecules were closely related. Although there are notable similarities in the structure of all these MAPK family members, there also exist some specific differences, which make the basis for different MAPKs responding to different extracellular stimuli. Some key structures, such as Loop 12, have been proved to play an important role in upstream kinase selection, substrate specificity and subcellular localization of MAPKs. Further studies of MAPKs on the relationship between the biological function and conformation will be helpful to the invention of novel MAPK inhibitors for the therapy of some critical diseases.