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A requirement for rac1 in the PDGF‐stimulated migration of fibroblasts and vascular smooth cells
Author(s) -
Doanes A. Masharn,
Irani Kaikobad,
GoldschmidtClermont Pascal J.,
Finkel Toren
Publication year - 1998
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/15216549800202652
Subject(s) - rac1 , platelet derived growth factor receptor , microbiology and biotechnology , chemistry , platelet derived growth factor , cancer research , signal transduction , biology , biochemistry , growth factor , receptor
Rac1 is a member of the Rho family of small GTPases. Although rac1 has been demonstrated to regulate the cytoskeleton, relatively little is known regarding its role in directional migration of mammalian cells. To address this issue, we have used recombinant adenoviruses to transiently express in fibroblasts either a dominant negative (N17rac1) or constitutively active (V12rac1) isoform of the small GTP‐binding protein rac1. Expression of N17rac1 is demonstrated to inhibit PDGF‐stimulated migration of rat fibroblasts. Surprisingly, expression of V12rac1 also inhibited, albeit to a lesser degree, the chemotactic response to PDGF. In contrast, expression of N17rac1 had no effect on PDGF stimulation of mitogen activated protein kinase (MAPK) or the adherence of cells to plastic or fibronectin coated surfaces. Similar to what was observed in fibroblasts, expression of N17rac1 inhibited the PDGF‐stimutated migration of primary vascular smooth muscle cells. These results identify rac1 as an important downstream mediator of PDGF‐induced chemotaxis.