Lopez-Ilasaca M
Max-Planck-Research Unit Molecular Cell Biology, Medical Faculty, University of Jena, Germany.
Biochem Pharmacol. 1998 Aug 1;56(3):269-77. doi: 10.1016/s0006-2952(98)00059-8.
Heterotrimeric GTP-binding protein (G-protein)-coupled receptors are able to induce a variety of responses including cell proliferation, differentiation, and activation of several intracellular kinase cascades. Prominent among these kinases are the activation of mitogen-activated protein (MAP) kinase, including the extracellular signal-regulated kinases (ERKs), ERK1 and ERK2 (p44mapk and p42mapk, respectively); stress-activated protein kinases (SAPKs/JNKs); and p38 kinase. These receptors signal through G-proteins. Recent data have shown that the activation of mitogen-activated protein/ERK kinase induced by G-protein-coupled receptors is mediated by both Galpha and Gbetagamma subunits involving a common signaling pathway with receptor-tyrosine-kinases. Gbetagamma-mediated mitogen-activated protein kinase activation is mediated by activation of phosphoinositide 3-kinase, followed by a tyrosine phosphorylation event, and proceeds in a sequence of events that involve functional association among the adaptor proteins Shc, Grb2, and Sos. SAPKs/JNKs and p38 are able to be activated by Gbetagamma proteins in a pathway involving Rho family proteins including RhoA, Rac1, and Cdc42.
异三聚体GTP结合蛋白（G蛋白）偶联受体能够诱导多种反应，包括细胞增殖、分化以及激活多个细胞内激酶级联反应。这些激酶中较为突出的是丝裂原活化蛋白（MAP）激酶的激活，包括细胞外信号调节激酶（ERKs），即ERK1和ERK2（分别为p44mapk和p42mapk）；应激激活蛋白激酶（SAPKs/JNKs）；以及p38激酶。这些受体通过G蛋白进行信号传导。最近的数据表明，G蛋白偶联受体诱导的丝裂原活化蛋白/ERK激酶激活是由Gα和Gβγ亚基介导的，涉及与受体酪氨酸激酶共同的信号通路。Gβγ介导的丝裂原活化蛋白激酶激活是由磷脂酰肌醇3激酶的激活介导的，随后是酪氨酸磷酸化事件，并按一系列事件进行，这些事件涉及衔接蛋白Shc、Grb2和Sos之间的功能关联。SAPKs/JNKs和p38能够在涉及Rho家族蛋白（包括RhoA、Rac1和Cdc42）的途径中被Gβγ蛋白激活。
