Dephosphorylation of receptor tyrosine kinases as target of regulation by radiation, oxidants or alkylating agents
Dephosphorylation of receptor tyrosine kinases as target of regulation by radiation, oxidants or alkylating agents
复制标题
DOI：
10.1002/j.1460-2075.1996.tb00916.x
复制
发表时间：
1996-10-01
期刊：
影响因子：
11.4
通讯作者：
Herrlich, P
中科院分区：
文献类型：
--
作者：
Knebel, A;Rahmsdorf, HJ;Herrlich, P
几种非生理试剂如辐射、氧化剂和烷化剂诱导质膜内侧的许多受体酪氨酸激酶（RTK）和蛋白酪氨酸激酶的配体非依赖性活化（例如Devary等，1992; Sachsenmaier等，1994; Schieven等人，一九九一年; Coffer等，1995），在此，我们显示了表皮生长因子受体（EGFR）活化的额外证据，并且我们显示了v-ErbB、ErbB 2和血小板衍生生长因子受体的活化。作为共同的作用原理，诱导剂如UVC、UVB、UVA、过氧化氢和碘乙酰胺在硫醇敏感性和低分子量的细胞中抑制受体酪氨酸去磷酸化，除了SH-烷基化剂之外，在Triton X-100存在下，EGFR去磷酸化也可以通过这些非生理性试剂在分离的质膜中以可逆方式调节。此外，底物（EGFR）和磷酸酶已经分离：已经用表皮生长因子（EGF）处理并且其去磷酸化酶已经被碘乙酰胺永久破坏的细胞的膜制备物可以与来自重建EGFR去磷酸化的未处理细胞的膜制备物混合。这种去磷酸化可以通过UV和硫醇试剂在体外调节。我们得出结论，RTK表现出显著的自发蛋白激酶活性;几种不利试剂靶向膜结合蛋白酪氨酸磷酸酶携带的必需SH基团。
Several non-physiologic agents such as radiation, oxidants and alkylating agents induce ligand-independent activation of numerous receptor tyrosine kinases (RTKs) and of protein tyrosine kinases at the inner side of the plasma membrane (e.g. Devary et al,, 1992; Sachsenmaier ct al., 1994; Schieven et al., 1991; Coffer ct al,, 1995), Here we show additional evidence for the activation of epidermal growth factor receptor (EGFR), and we show activation of v-ErbB, ErbB2 and platelet-derived growth factor receptor, As a common principle of action the inducing agents such as UVC, UVB, UVA, hydrogen peroxide and iodoacetamide inhibit receptor tyrosine dephosphorylation in a thiol-sensitive and, with the exception of the SH-alkylating agent, reversible manner, EGFR dephosphorylation can also be modulated by these non-physiologic agents in isolated plasma membranes in the presence of Triton X-100. Further, substrate (EGFR) and phosphatase have been separated: a membrane preparation of cells that have been treated with epidermal growth factor (EGF) and whose dephosphorylating enzymes have been permanently destroyed by iodoacetamide can be mixed with a membrane preparation from untreated cells which reestablishes EGFR dephosphorylation. This dephosphorylation can be modulated bl vitro by UV and thiol agents, We conclude that RTKs exhibit significant spontaneous protein kinase activity; several adverse agents target (an) essential SH-group(s) carried by (a) membrane-bound protein tyrosine phosphatase(s).