PAK1 and PAK2 have different roles in HGF-induced morphological responses

Cell Signal. 2009 Dec;21(12):1738-47. doi: 10.1016/j.cellsig.2009.07.005. Epub 2009 Jul 21.

Abstract

Hepatocyte growth factor (HGF) stimulates dissociation of epithelial cells (scattering) and cell migration. Several Rho GTPases are required for HGF-induced scattering. PAK1 and PAK2 are members of the p21-activated kinase (PAK) family of serine/threonine kinases, and are activated by the Rho GTPases Rac and Cdc42. Here we investigate the contributions of PAK1 and PAK2 to HGF-induced motile response. HGF stimulates phosphorylation of PAK1 and PAK2. Knockdown of PAK1 inhibits HGF-stimulated migration and loss of cell-cell junctions in DU145 prostate carcinoma cells, whereas knockdown of PAK2 enhances loss of cell-cell junctions and increases lamellipodium extension but does not affect migration speed. On the other hand, in PC3 prostate carcinoma cells, which lack cell-cell junctions, knockdown of PAK1 or PAK2 reduces HGF-stimulated migration. PAK2 knockdown increases phosphorylation of PAK1, indicating that PAK2 provides a negative feedback on PAK1. We hypothesise that PAK2 acts in part via PAK1 to regulate HGF-induced scattering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma / enzymology*
  • Cell Line, Tumor
  • Cell Movement*
  • Gene Knockdown Techniques
  • Hepatocyte Growth Factor / metabolism*
  • Humans
  • Intercellular Junctions / metabolism
  • Male
  • Phosphorylation
  • Prostatic Neoplasms / enzymology*
  • p21-Activated Kinases / genetics
  • p21-Activated Kinases / metabolism*

Substances

  • Hepatocyte Growth Factor
  • PAK1 protein, human
  • PAK2 protein, human
  • p21-Activated Kinases