sGSK group, Astar Neuroscience Research Partnership, Proteos Building, 61 Biopolis Drive, Singapore 138673, Singapore.
EMBO Rep. 2012 Jun 29;13(7):653-9. doi: 10.1038/embor.2012.75.
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 auto-inhibitory 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.
p21 激活激酶 (PAKs) 是后生动物、真菌和原生动物中发现的 Cdc42 效应物。它们分为 PAK1 样 (I 组) 或 PAK4 样 (II 组) 激酶。人 PAK4 广泛表达，其调节机制尚不清楚。我们发现 PAK4 被一个新鉴定的自身抑制结构域 (AID) 强烈抑制，该结构域由 20 到 68 个氨基酸组成，与其他 PAK 的 AID 在进化上有关。与 I 组激酶不同，PAK4 在激活环上的 Ser474 上持续磷酸化，但处于非活性状态，直到与 Cdc42 结合。因此，II 组 PAK 是通过 AID 中的构象变化而不是 A 环磷酸化来调节的。
