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Synectin‐dependent suppression of basal Rac1 activity is reversed by a signaling pathway involving PKCalpha and RhoG
Author(s) -
Elfenbein Arye,
Simons Michael
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb11-d
Subject(s) - rac1 , microbiology and biotechnology , signal transduction , fibroblast growth factor , phosphorylation , tyrosine phosphorylation , angiogenesis , guanine nucleotide exchange factor , chemistry , biology , receptor , cancer research , biochemistry
Endothelial cell migration, an early event in angiogenesis, is potently stimulated by fibroblast growth factors (FGFs). FGF signaling may proceed via their high‐affinity tyrosine kinase receptors, or via heparan sulfate proteoglycans, including syndecan‐4 (S4). In this study, we explored the signaling events by which FGF2 elicits a migratory response in endothelial cells, focusing on the role of a Rac1‐activating small GTPase, RhoG. We found that FGF2 activates Rac1 in migrating endothelial cells via a pathway involving RhoG. FGF2 does not require its high‐affinity receptors to activate this pathway; RhoG and Rac1 are activated by the oligomerization of S4 alone. Furthermore, a signaling complex of S4 and its binding partner, synectin, is initially required to maintain low baseline levels of Rac1 activity in serum‐starved endothelial cells. When FGF2 is added to these cells, the described Rac1 suppression is alleviated by a pathway requiring PKCalpha and one of its phosphorylation targets, Rho guanine dissociation inhibitor‐1 (RhoGDI‐1). Collectively, these data outline a novel role for S4 and synectin in the suppression of Rac1 activity, and identify key enzymes mediating the reversal of this suppression in stimulated, migrating cells.