Corbalan-Garcia S, Degenhardt K R, Bar-Sagi D
Department of Molecular Genetics and Microbiology, State University of New York at Stony Brook, 11794-8621, USA.
Oncogene. 1996 Mar 7;12(5):1063-8.
Activation of Ras by a number of receptor tyrosine kinases is mediated by the guanine nucleotide exchange factor Sos. This activation is thought to occur as a result of the recruitment to the plasma membrane of a complex consisting of Sos and the adaptor molecule Grb2. Growth factor stimulation has been shown to induce the rapid phosphorylation of Sos on serine and threonine residues. In rat L6 cells, insulin-induced Sos phosphorylation is accompanied by a partial dissociation of the Grb2-Sos complex. In this study we have investigated the relationship between Sos phosphorylation and Grb2 association. To this end, we have utilized cAMP because it has been demonstrated that elevation of cytoplasmic levels of cAMP inhibits growth factor-induced Sos phosphorylation. We show that in rat L6 cells, cAMP treatment prevents both the insulin-stimulated Sos phosphorylation and Grb2 dissociation. However, cAMP treatment has no effect on the duration of insulin-induced Ras activation. These results suggest that the kinetics of Ras activation are independent of the phosphorylation-induced dissociation of Sos from Grb2.
许多受体酪氨酸激酶对Ras的激活是由鸟嘌呤核苷酸交换因子Sos介导的。这种激活被认为是由于由Sos和衔接分子Grb2组成的复合物被招募到质膜上的结果。生长因子刺激已被证明可诱导Sos在丝氨酸和苏氨酸残基上快速磷酸化。在大鼠L6细胞中，胰岛素诱导的Sos磷酸化伴随着Grb2-Sos复合物的部分解离。在本研究中，我们研究了Sos磷酸化与Grb2结合之间的关系。为此，我们利用了cAMP，因为已经证明细胞质中cAMP水平的升高会抑制生长因子诱导的Sos磷酸化。我们表明，在大鼠L6细胞中，cAMP处理可防止胰岛素刺激的Sos磷酸化和Grb2解离。然而，cAMP处理对胰岛素诱导的Ras激活持续时间没有影响。这些结果表明，Ras激活的动力学与Sos从Grb2的磷酸化诱导解离无关。
