Evidence for a Ras-dependent extracellular signal-regulated protein kinase (ERK) cascade.
Evidence for a Ras-dependent extracellular signal-regulated protein kinase (ERK) cascade.
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Ras 依赖性细胞外信号调节蛋白激酶 (ERK) 级联的证据。
DOI：
10.1073/pnas.89.15.6924
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发表时间：
1992
影响因子：
11.1
通讯作者：
Cobb,MH
中科院分区：
文献类型：
--
作者：
Robbins,DJ;Cheng,M;Zhen,E;Vanderbilt,CA;Feig,LA;Cobb,MH
小的GTP结合蛋白RAS似乎是酪氨酸激酶诱导的转化和分化所必需的。RAS的要求可能仅限于少数几个酪氨酸激酶调节的信号通路，或者可能对所有的酪氨酸激酶作用都是通用的。由于RAS和微管相关蛋白2激酶ERK1和ERK2都参与了导致轴突生长的事件，我们探讨了RAS和ERKs可能位于同一信号通路上的可能性。利用含有显性抑制RAS突变体(S17N-RAS(H))的PC-12大鼠肾上腺嗜铬细胞瘤细胞系，我们发现神经生长因子刺激ERK级联反应需要RAS，而异源三聚体G蛋白激活剂AlF4-显然不需要RAS。在这个级联中，RAS似乎位于ERK激活子的上游，这增加了RAS可能直接调节丝氨酸/苏氨酸蛋白激酶的有趣的可能性。
The small GTP-binding protein Ras appears to be required for transformation and differentiation induced by tyrosine kinases. The Ras requirement may be limited to a few tyrosine kinase-regulated signaling pathways or may be universal for all tyrosine kinase actions. Because both Ras and the microtubule-associated protein 2 kinases ERK1 and ERK2 have been implicated in events that lead to neurite outgrowth, we explored the possibility that Ras and ERKs may lie on the same signaling pathway. Utilizing PC-12 rat adrenal pheochromocytoma cell lines that contain a dominant inhibitory Ras mutant (S17N-Ras(H)), we found that Ras was required for stimulation of the ERK cascade by nerve growth factor but apparently not by the heterotrimeric G protein activator AlF4-. Within this cascade, Ras appears to be upstream of an ERK activator, raising the intriguing possibility that Ras may directly regulate a serine/threonine protein kinase.