Phosphorylation and regulation of Raf by Akt (protein kinase B)
Phosphorylation and regulation of Raf by Akt (protein kinase B)
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DOI：
10.1126/science.286.5445.1741
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发表时间：
1999-11-26
期刊：
影响因子：
56.9
通讯作者：
Moelling, K
中科院分区：
文献类型：
--
作者：
Zimmermann, S;Moelling, K
蛋白激酶Raf的激活可导致相反的细胞反应，如增殖、生长停滞、凋亡、分化。Akt（蛋白激酶B），一个不同的信号通路，也调节这些反应的成员，与Raf相互作用，并磷酸化这种蛋白在其调节结构域中的高度保守的丝氨酸残基在体内。Akt对Raf的磷酸化抑制了Raf-MEK-ERK信号通路的激活，并将人乳腺癌细胞系中的细胞反应从细胞周期停滞转变为增殖。这些观察结果为Raf和Akt水平上两条信号通路之间的串扰提供了分子基础。
Activation of the protein kinase Raf can lead to opposing cellular responses such as proliferation, growth arrest, apoptosis, br differentiation. Akt (protein kinase B), a member of a different signaling pathway that also regulates these responses, interacted with Raf and phosphorylated this protein at a highly conserved serine residue in its regulatory domain in vivo. This phosphorylation of Raf by Akt inhibited activation of the Raf-MEK-ERK signaling pathway and shifted the cellular response in a human breast cancer cell line from cell cycle arrest to proliferation. These observations provide a molecular basis for cross talk between two signaling pathways at the level of Raf and Akt.