p21 激活激酶 1（PAK1）能够以一种激酶非依赖性的方式促进 ERK 的激活。
p21-activated kinase 1 (PAK1) can promote ERK activation in a kinase-independent manner.
机构信息
Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
出版信息
J Biol Chem. 2013 Jul 5;288(27):20093-9. doi: 10.1074/jbc.M112.426023. Epub 2013 May 7.
Abstract
PAK1 plays an important role in proliferation and tumorigenesis, at least partially by promoting ERK phosphorylation of C-RAF (Ser-338) or MEK1 (Ser-298). We observed how that overexpression of a kinase-dead mutant form of PAK1 increased phosphorylation of MEK1/2 (Ser-217/Ser-221) and ERK (Thr-202/Tyr-204), although phosphorylation of B-RAF (Ser-445) and C-RAF (Ser-338) remained unchanged. Furthermore, increased activation of the PAK1 activator Rac1 induced the formation of a triple complex of Rac1, PAK1, and MEK1 independent of the kinase activity of PAK1. These data suggest that PAK1 can stimulate MEK activity in a kinase-independent manner, probably by serving as a scaffold to facilitate interaction of C-RAF.
摘要
PAK1 在增殖和肿瘤发生中发挥重要作用，至少部分通过促进 ERK 对 C-RAF（Ser-338）或 MEK1（Ser-298）的磷酸化。我们观察到，过表达激酶失活突变形式的 PAK1 增加了 MEK1/2（Ser-217/Ser-221）和 ERK（Thr-202/Tyr-204）的磷酸化，尽管 B-RAF（Ser-445）和 C-RAF（Ser-338）的磷酸化保持不变。此外，PAK1 激活剂 Rac1 的激活增加导致 Rac1、PAK1 和 MEK1 的三聚体复合物的形成，这与 PAK1 的激酶活性无关。这些数据表明 PAK1 可以以激酶非依赖的方式刺激 MEK 活性，可能通过作为支架促进 C-RAF 的相互作用。
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