Group I and II mammalian PAKs have different modes of activation by Cdc42

被引：95

作者：

Baskaran, Yohendran ^{[1
]}

Ng, Yuen-Wai ^{[1
]}

Selamat, Widyawilis ^{[1
]}

Ling, Felicia Tay Pei ^{[1
]}

Manser, Ed ^{[1
,2
]}

机构：

[1] Astar Neurosci Res Partnership, SGSK Grp, Singapore 138673, Singapore

[2] Inst Med Biol, Singapore 138648, Singapore

来源：

EMBO REPORTS | 2012年 / 13卷 / 07期

关键词：

cytoskeleton; PAK4; Cdc42; phosphorylation; P21-ACTIVATED KINASE; EPITHELIAL-CELLS; ALPHA-PAK; PROTEIN; REVEALS; MIGRATION; TURNOVER; ADHESION; INVASION; RECEPTOR;

D O I：

10.1038/embor.2012.75

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

p21-activated kinases (PAKs) are Cdc42 effectors found in metazoans, fungi and protozoa. They are subdivided into PAK1-like (group I) or PAK4-like (group II) kinases. Human PAK4 is widely expressed and its regulatory mechanism is unknown. We show that PAK4 is strongly inhibited by a newly identified autoinhibitory domain (AID) formed by amino acids 20 to 68, which is evolutionarily related to that of other PAKs. In contrast to group I kinases, PAK4 is constitutively phosphorylated on Ser 474 in the activation loop, but held in an inactive state until Cdc42 binding. Thus, group II PAKs are regulated through conformational changes in the AID rather than A-loop phosphorylation.

引用

页码：653 / 659

页数：7

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