Requirement of Ras-GTP-Raf complexes for activation of Raf-1 by protein kinase C
Requirement of Ras-GTP-Raf complexes for activation of Raf-1 by protein kinase C
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DOI：
10.1126/science.280.5360.109
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发表时间：
1998-04-03
期刊：
影响因子：
56.9
通讯作者：
Marshall, CJ
中科院分区：
文献类型：
--
作者：
Marais, R;Light, Y;Marshall, CJ
受体酪氨酸激酶介导的Raf-1蛋白激酶的激活与小鸟苷三磷酸（GTP）结合蛋白Ras偶联，相比之下，蛋白激酶C （PKC）介导的Raf-1的激活被认为是Ras独立的，然而，COS细胞中PKC的刺激导致Ras的激活并形成含有活性Raf-1的Ras-Raf-1复合物，Raf-1突变阻止其与Ras的关联，从而阻断了PKC对Raf-1的激活。PKC对Raf-1的激活未被显性阴性Ras阻断，表明PKC激活Ras的机制不同于受体酪氨酸激酶激活的机制。
Receptor tyrosine kinase-mediated activation of the Raf-1 protein kinase is coupled to the small guanosine triphosphate (GTP)-binding protein Ras, By contrast, protein kinase C (PKC)-mediated activation of Raf-1 is thought to be Ras independent, Nevertheless, stimulation of PKC in COS cells led to activation of Ras and formation of Ras-Raf-1 complexes containing active Raf-1, Raf-1 mutations that prevent its association with Ras blocked activation of Raf-1 by PKC, However, the activation of Raf-1 by PKC was not blocked by dominant negative Ras, indicating that PKC activates Ras by a mechanism distinct from that initiated by activation of receptor tyrosine kinases.