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

TY - JOUR

T1 - PAK1 and PAK2 have different roles in HGF-induced morphological responses

AU - Bright, Michael D.

AU - Garner, Andrew P.

AU - Ridley, Anne J.

PY - 2009/12

Y1 - 2009/12

N2 - 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 PAKI, indicating that PAK2 provides a negative feedback on PAK1. We hypothesise that PAK2 acts in part via PAKI to regulate HGF-induced scattering. (C) 2009 Elsevier Inc. All rights reserved.

AB - 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 PAKI, indicating that PAK2 provides a negative feedback on PAK1. We hypothesise that PAK2 acts in part via PAKI to regulate HGF-induced scattering. (C) 2009 Elsevier Inc. All rights reserved.

U2 - 10.1016/j.cellsig.2009.07.005

DO - 10.1016/j.cellsig.2009.07.005

M3 - Article

VL - 21

SP - 1738

EP - 1747

JO - Cellular Signalling

JF - Cellular Signalling

IS - 12

ER -