Src kinase regulation by phosphorylation and dephosphorylation
Src kinase regulation by phosphorylation and dephosphorylation
复制标题
DOI：
10.1016/j.bbrc.2005.03.012
复制
发表时间：
2005-05-27
影响因子：
3.1
通讯作者：
Roskoski, R
中科院分区：
文献类型：
--
作者：
Roskoski, R
Re和Src家族蛋白酪氨酸激酶是调节细胞分化、运动、增殖和存活的关键蛋白。最初描述的Src的磷酸化位点包括由自磷酸化产生的激活的磷酸酪氨酸416，以及由C-末端的Src激酶(CSK)和CSK同源激酶的磷酸化产生的抑制的磷酸酪氨酸527。磷酸化酪氨酸527的去磷酸化增加了Src激酶的活性。候选的磷酸酪氨酸527磷酸酶包括细胞质PTP1B、SHP1和Shp2，跨膜酶包括CD45、PTPα。PTP epsilon和PTP lambda。磷酸酪氨酸416的去磷酸化降低了Src激酶的活性。到目前为止，人类PTP-BAS的小鼠同源物PTP-BL已经被证明以一种调节的方式使磷酸酪氨酸416去磷酸化。血小板衍生生长因子受体蛋白-酪氨酸激酶介导了Src Tyr138的磷酸化：这种磷酸化。对Src激酶活性无直接影响。血小板衍生生长因子受体和ErbB2/HER2生长因子受体蛋白酪氨酸激酶介导了Src Tyr213的磷酸化和Src激酶活性的激活。SRC激酶也是蛋白-丝氨酸/苏氨酸激酶的底物，包括蛋白激酶C(Ser12)、蛋白激酶A(Ser17)和CDK1/cdc2(Thr34、Thr46和Ser72)。在三种蛋白-丝氨酸/苏氨酸激酶中，只有CDK1/cdc2的磷酸化能增加Src激酶的活性。虽然目前已有大量关于催化Src磷酸酪氨酸527的磷酸蛋白磷酸酶的信息，但介导磷酸酪氨酸138和213以及磷酸丝氨酸和磷酸苏氨酸残基的磷酸酶的性质尚未确定。(C)2005 Elsevier Inc.保留所有权利。
Re and Src-family protein-tyrosine kinases are regulatory proteins that play key roles in cell differentiation, motility, proliferation, and survival. The initially described phosphorylation sites of Src include an activating phosphotyrosine 416 that results from autophosphorylation, and an inhibiting phosphotyrosine 527 that results from phosphorylation by C-terminal Src kinase (Csk) and Csk homologous kinase. Dephosphorylation of phosphotyrosine 527 increases Src kinase activity. Candidate phosphotyrosine 527 phosphatases include cytoplasmic PTP1B, Shp1 and Shp2, and transmembrane enzymes include CD45, PTP alpha. PTP epsilon, and PTP lambda. Dephosphorylation of phosphotyrosine 416 decreases Src kinase activity. Thus far PTP-BL, the mouse homologue of human PTP-BAS, has been shown to dephosphorylate phosphotyrosine 416 in a regulatory fashion. The platelet-derived growth factor receptor protein-tyrosine kinase mediates the phosphorylation of Src Tyr138: this phosphorylation. has no direct effect on Src kinase activity. The platelet-derived growth factor receptor and the ErbB2/HER2 growth factor receptor protein-tyrosine kinases mediate the phosphorylation of Src Tyr213 and activation of Src kinase activity. Src kinase is also a substrate for protein-serine/threonine kinases including protein kinase C (Ser12), protein kinase A (Ser17), and CDK1/cdc2 (Thr34, Thr46, and Ser72). Of the three protein-serine/threonine kinases, only phosphorylation by CDK1/cdc2 has been demonstrated to increase Src kinase activity. Although considerable information on the phosphoprotein phosphatases that catalyze the hydrolysis of Src phosphotyrosine 527 is at hand, the nature of the phosphatases that mediate the hydrolysis of phosphotyrosine 138 and 213, and phosphoserine and phosphothreonine residues has not been determined. (c) 2005 Elsevier Inc. All rights reserved.