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Phosphorylation of Vasodilator‐Stimulated Phosphoprotein (VASP) Regulates Contractility of Airway Smooth Muscle (ASM) Tissues by Regulating Actin Dynamics
Author(s) -
Wu Yidi,
Vemuri Bhargavi,
Gunst Susan J
Publication year - 2011
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.25.1_supplement.1115.1
Subject(s) - phosphoprotein , contractility , phosphorylation , microbiology and biotechnology , actin , vasodilation , chemistry , airway , smooth muscle , medicine , biology , anesthesia
VASP is an actin regulatory protein that plays a role in numerous cellular processes. VASP is a substrate for protein kinase A, which catalyzes its phosphorylation at ser157. Contractile stimulation of ASM initiates actin polymerization which is required for force development. We hypothesized that VASP might contribute to the regulation of actin dynamics and contraction of ASM tissues. Acetylcholine (ACh) stimulation dramatically increased VASP phosphorylation on Ser157, which was inhibited by a PKC inhibitor. The expression of EGFP‐VASP Ser157A mutant protein in ASM tissues decreased endogenous VASP ser157 phosphorylation, depressed contractile force in response to ACh by 50%, and inhibited ACh‐induced actin polymerization. MLC phosphorylation was not affected. Immunofluorescence studies of dissociated ASM cells showed that ACh stimulated the recruitment of endogenous VASP protein to the cell membrane. Ser157 phosphorylated VASP was localized at the cell membrane and increased at the membrane after ACh stimulation. Expression of VASP ser157A mutant inhibited recruitment of endogenous VASP protein to the membrane. We conclude that ACh regulates VASP ser157 phosphorylation in ASM tissues through a PKC‐dependent pathway, and that VASP phosphorylation at ser 157 affects contractile force development by participating in the regulation of ACh‐stimulated cortical actin polymerization.