INHIBITION BY CAMP OF RAS-DEPENDENT ACTIVATION OF RAF
INHIBITION BY CAMP OF RAS-DEPENDENT ACTIVATION OF RAF
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DOI：
10.1126/science.7694367
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发表时间：
1993-11-12
期刊：
影响因子：
56.9
通讯作者：
MCCORMICK, F
中科院分区：
文献类型：
--
作者：
COOK, SJ;MCCORMICK, F
Raf和细胞外信号调节激酶（ERK）（或丝裂原活化蛋白激酶）的激活是促有丝分裂信号传导的关键事件，但对与其他信号传导途径的相互作用知之甚少。在暴露于表皮生长因子（EGF）或溶血磷脂酸的Rat 1细胞中，提高细胞内环腺苷酸（cAMP）水平的药物阻断了DNA合成和信号转导。 在EGF的情况下，受体酪氨酸激酶活性和与信号分子Grb 2和Shc的关联不受cAMP的影响。 同样，Ras的鸟苷5 '-三磷酸结合形式的EGF依赖性积累不受影响。 相反，Raf-1和ERK激酶的激活被抑制。因此，cAMP似乎通过阻止Raf-1的Ras依赖性激活来抑制Ras的信号传递。
Activation of the Raf and extracellular signal-regulated kinases (ERKs) (or mitogen-activated protein kinases) are key events in mitogenic signaling, but little is known about interactions with other signaling pathways. Agents that raise levels of intracellular cyclic adenosine 3',5'-monophosphate (cAMP) blocked DNA synthesis and signal transduction in Rat1 cells exposed to epidermal growth factor (EGF) or lysophosphatidic acid. In the case of EGF, receptor tyrosine kinase activity and association with the signaling molecules Grb2 and Shc were unaffected by cAMP. Likewise, EGF-dependent accumulation of the guanosine 5'-triphosphate-bound form of Ras was unaffected. In contrast, activation of Raf-1 and ERK kinases was inhibited. Thus, cAMP appears to inhibit signal transmission from Ras by preventing Ras-dependent activation of Raf-1.