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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Gene Expression Regulation, Enzymologic*
  • Humans
  • Phosphorylation
  • Signal Transduction*
  • Substrate Specificity
  • p21-Activated Kinases / genetics
  • p21-Activated Kinases / metabolism*

Substances

  • p21-Activated Kinases