An oncogenic kinase: putting PAK5 forward

Expert Opin Ther Targets. 2014 Jul;18(7):807-15. doi: 10.1517/14728222.2014.918103. Epub 2014 May 29.

Abstract

Introduction: Overexpression of p21-activated kinase 5 (PAK5) is discovered in many tumors, probably due to its regulation in cytoskeleton, antiapoptosis and proliferation. A better understanding of the modulation mechanisms of PAK5 is needed for the development of tumor treatment where current therapeutics is inadequate.

Areas covered: This review discusses the current understanding of PAK5 functions as an oncogenic kinase in tumor cellular regulation. Mechanisms of action and molecular pathways involved in cytoskeleton regulation, antiapoptosis and proliferation of tumors are discussed.

Expert opinion: PAKs are serine/threonine kinases and downstream effectors for Cdc42 and Rac, the subfamilies of Rho small GTPases. PAK5 shares sequence identities in p21-GTPase-binding domain and kinase domain and is completely different in other regions compared with other PAKs. Overexpression of PAK5 has been found in several tumors, probably due to its contribution to proliferation, cytoskeleton and anti-apoptosis. Additional regulation mechanisms which are independent of Rho GTPases also indicate that PAK5 functions as a special signal molecule in cellular signaling pathways of tumor progression.

Keywords: antiapoptosis; invasion; metastasis; p21-activated kinase 5; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Cytoskeleton / metabolism
  • G1 Phase Cell Cycle Checkpoints
  • Humans
  • Mitochondria / metabolism
  • Neoplasms / metabolism*
  • p21-Activated Kinases / metabolism*

Substances

  • PAK5 protein, human
  • p21-Activated Kinases