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Overexpression of WAVE‐1 inhibits cell migration induced by PDGF via PKA signaling without affecting VASP ser157 phosphorylation
Author(s) -
Zhang DeLing,
OuYang JingPing,
Zhang YaHui,
Wang Nian,
Xiong Ming,
Zhang YeMin
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.a915
Subject(s) - cell migration , microbiology and biotechnology , phosphorylation , platelet derived growth factor receptor , cell , phosphoprotein , motility , chemistry , lamellipodium , cell growth , biology , biochemistry , growth factor , receptor
WAVE‐1 protein acts as a member of AKAPs family, which serve to associate PKA with various components of actin cytoskeleton so as to modulate cell shape and movement. Vasodilator‐stimulated phosphoprotein (VASP) is a major substrate for PKA, which appears to be critical for its function during cell migration. To investigate the effect of WAVE‐1 on cell migration and the underlying regulation mechanism, we developed stable WAVE‐1 overexpressing ECV304 cell line. The study show PDGF stimulate cell migration of empty vector control through transwell migration assay, accompanied with enhanced PKA activity and increased VASP ser 157 site phosphorylation. In contrast,cells overexpressed WAVE‐1 show diminished cell migration and 3‐fold higher PKA in response to PDGF. However, inhibition of cell migration in this condition was partly reversed in the presence of St‐Ht31(PKA RII‐AKAP selectivity anchoring inhibitor peptide). Meanwhile, PKA activity was attenuated by St‐Ht31.Cells overexpressed WAVE‐1 and control show very similar VASP phosphorylation after PDGF stimulation, which did not obviously changed by adding St‐Ht31 yet. Nevertheless, We observed transfecting VASP ser 157 site mutant into cells overexpressed WAVE‐1 lead to further diminution of migration under PDGF treatment. These findings suggest that overexpressed WAVE‐1 inhibits cell migration induced by PDGF,which is correlated with hyper‐activation of PKA. It seems that PKA‐ mediated VASP phosphorylation was not involved in negative regulation of cell migration but help to maintain stable cell motility ability in part. (The research is supported by national natural science foundation of China granted NO.30470680)