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J Biol Chem. 2015 May 22;290(21):12975-83. doi: 10.1074/jbc.R115.650416. Epub 2015 Apr 8.

Signaling, Regulation, and Specificity of the Type II p21-activated Kinases.

Author information

1
From the Departments of Pharmacology and.
2
Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520.
3
From the Departments of Pharmacology and titus.boggon@yale.edu.

Abstract

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.

KEYWORDS:

CDC42; Ras-related C3 botulinum toxin substrate 1 (Rac1); protein structure; serine/threonine protein kinase; signal transduction

PMID:
25855792
PMCID:
PMC4505552
DOI:
10.1074/jbc.R115.650416
[Indexed for MEDLINE]
Free PMC Article

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