期刊
CELLULAR SIGNALLING
卷 21, 期 12, 页码 1738-1747出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2009.07.005
关键词
PAK; HGF; Cell migration; Prostate cancer cells; Cell-cell junctions; Rho GTPases
类别
资金
- Ludwig Institute for Cancer Research
- Fondation Bettencourt Schueller
- European Union [LSHG-CT-2003-502935]
- BBSRC CASE PhD studentship with AstraZeneca
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.
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