C-TAK1 regulates Ras signaling by phosphorylating the MAPK scaffold, KSR1
C-TAK1 regulates Ras signaling by phosphorylating the MAPK scaffold, KSR1
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DOI：
10.1016/s1097-2765(01)00383-5
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发表时间：
2001-11-01
期刊：
影响因子：
16
通讯作者：
Morrison, DK
中科院分区：
文献类型：
--
作者：
Müller, J;Ory, S;Morrison, DK
Ras 激酶抑制因子 (KSR) 是 Ras 途径的保守成分，可直接与 MEK 和 MAPK 相互作用。在这里，我们表明，KSR1 在生长因子处理下从细胞质易位到细胞表面，并且该过程受到 Cdc25C 相关激酶 1 (C-TAK1) 的调节。 C-TAK1 与哺乳动物 KSR1 组成型结合，并磷酸化丝氨酸 392，以在未刺激的细胞中赋予 KSR1 14-3-3 结合和细胞质隔离。响应信号激活，S392 的磷酸化状态降低，使 KSR1 复合物与质膜上激活的 Ras 和 Raf-1 共定位，从而促进 MEK 和 MAPK 激活所需的磷酸化反应。
Kinase suppressor of Ras (KSR) is a conserved component of the Ras pathway that interacts directly with MEK and MAPK. Here we show that KSR1 translocates from the cytoplasm to the cell surface in response to growth factor treatment and that this process is regulated by Cdc25C-associated kinase 1 (C-TAK1). C-TAK1 constitutively associates with mammalian KSR1 and phosphorylates serine 392 to confer 14-3-3 binding and cytoplasmic sequestration of KSR1 in unstimulated cells. In response to signal activation, the phosphorylation state of S392 is reduced, allowing the KSR1 complex to colocalize with activated Ras and Raf-1 at the plasma membrane, thereby facilitating the phosphorylation reactions required for the activation of MEK and MAPK.