Nakajima T, Fukamizu A, Takahashi J, Gage F H, Fisher T, Blenis J, Montminy M R
Department of Cellular and Molecular Physiology Harvard Medical School Boston, Massachusetts 02115, USA.
Cell. 1996 Aug 9;86(3):465-74. doi: 10.1016/s0092-8674(00)80119-1.
We have examined the mechanism by which growth factor-mediated induction of the Ras pathway interferes with signaling via the second messenger cAMP. Activation of cellular Ras with insulin or NGF stimulated recruitment of the S6 kinase pp90RSK to the signal-dependent coactivator CBP. Formation of the pp90RSK-CBP complex occurred with high stoichiometry and persisted for 6-8 hr following growth factor addition. pp90RSK specifically recognized the E1A-binding domain of the coactivator CBP. In addition, like E1A, binding of pp90RSK to CBP was sufficient to repress transcription of cAMP-responsive genes via the cAMP-inducible factor CREB. By contrast with its effects on the cAMP pathway, formation of the pp90RSK-CBP complex was required for induction of Ras-responsive genes. These results provide a demonstration of cross-coupling between two signaling pathways that occurs at the level of a signal-dependent coactivator.
我们已经研究了生长因子介导的Ras途径诱导干扰通过第二信使cAMP进行信号传导的机制。用胰岛素或神经生长因子（NGF）激活细胞Ras会刺激S6激酶pp90RSK募集到信号依赖性共激活因子CBP。pp90RSK-CBP复合物以高化学计量比形成，并且在添加生长因子后持续6-8小时。pp90RSK特异性识别共激活因子CBP的E1A结合结构域。此外，与E1A一样，pp90RSK与CBP的结合足以通过cAMP诱导因子CREB抑制cAMP反应性基因的转录。与其对cAMP途径的影响相反，诱导Ras反应性基因需要形成pp90RSK-CBP复合物。这些结果证明了在信号依赖性共激活因子水平上发生的两条信号通路之间的交叉偶联。
