Ha Byung Hak, Morse Elizabeth M, Turk Benjamin E, Boggon Titus J
From the Departments of Pharmacology and.
Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520.
J Biol Chem. 2015 May 22;290(21):12975-83. doi: 10.1074/jbc.R115.650416. Epub 2015 Apr 8.
The p21-activated kinases (PAKs) are a family of six serine/threonine kinases that act as key effectors of RHO family GTPases in mammalian cells. PAKs are subdivided into two groups: type I PAKs (PAK1, PAK2, and PAK3) and type II PAKs (PAK4, PAK5, and PAK6). Although these groups are involved in common signaling pathways, recent work indicates that the two groups have distinct modes of regulation and have both unique and common substrates. Here, we review recent insights into the molecular level details that govern regulation of type II PAK signaling. We also consider mechanisms by which signal transduction is regulated at the level of substrate specificity. Finally, we discuss the implications of these studies for clinical targeting of these kinases.
p21激活激酶（PAKs）是一个由六种丝氨酸/苏氨酸激酶组成的家族，它们在哺乳动物细胞中作为RHO家族GTP酶的关键效应器发挥作用。PAKs可分为两组：I型PAKs（PAK1、PAK2和PAK3）和II型PAKs（PAK4、PAK5和PAK6）。尽管这两组激酶参与共同的信号通路，但最近的研究表明，这两组激酶具有不同的调节模式，并且具有独特的和共同的底物。在这里，我们综述了关于调控II型PAK信号传导的分子水平细节的最新见解。我们还考虑了在底物特异性水平上调节信号转导的机制。最后，我们讨论了这些研究对这些激酶临床靶向治疗的意义。
