VASP phosphorylation at serine239 regulates the effects of NO on smooth muscle cell invasion and contraction of collagen.
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VASP phosphorylation at serine239 regulates the effects of NO on smooth muscle cell invasion and contraction of collagen. / Defawe, Olivier D; Kim, Sarah; Chen, Lihua; Huang, Daming; Kenagy, Richard D; Renné, Thomas; Walter, Ulrich; Daum, Günter; Clowes, Alexander W.
in: J CELL PHYSIOL, Jahrgang 222, Nr. 1, 1, 2010, S. 230-237.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - VASP phosphorylation at serine239 regulates the effects of NO on smooth muscle cell invasion and contraction of collagen.
AU - Defawe, Olivier D
AU - Kim, Sarah
AU - Chen, Lihua
AU - Huang, Daming
AU - Kenagy, Richard D
AU - Renné, Thomas
AU - Walter, Ulrich
AU - Daum, Günter
AU - Clowes, Alexander W
PY - 2010
Y1 - 2010
N2 - Nitric oxide triggers cGMP-dependent kinase-mediated phosphorylation of the actin regulator vasodilator-stimulated phosphoprotein (VASP) at residue serine239. The function of this phosphorylation for smooth muscle cell (SMC) adhesion, spreading, matrix contraction, and invasion is not well understood. We reconstituted VASP deficient SMC with wild-type VASP (wt-VASP) or VASP mutants that mimic "locked" serine239 phosphorylation (S239D-VASP) or "blocked" serine239 phosphorylation (S239A-VASP). Collagen gel contraction was reduced in S239D-VASP compared to S239A-VASP and wt-VASP expressing cells and nitric oxide (NO) stimulation decreased gel contraction of wt-VASP reconstituted SMC. Invasion of collagen was enhanced in S239D-VASP and NO-stimulated wild-type SMCs compared to S239A-VASP expressing cells. Expression of S239D-VASP impaired SMC attachment to collagen, reduced the number of membrane protrusions, and caused cell rounding compared to expression of S239A-VASP. Treatment of wt-VASP reconstituted SMCs with NO exerted similar effects as expression of S239D-VASP. As unstimulated cells were spreading on collagen S239A-VASP and wt-VASP localized to actin fibers whereas S239D-VASP was enriched in the cytosol. NO interferes with SMC invasion and contraction of collagen matrices. This requires phosphorylation of VASP on serine239, which reduces VASP binding to actin fibers. These findings support the conclusion that VASP phosphorylation at serine239 regulates cytoskeleton remodeling.
AB - Nitric oxide triggers cGMP-dependent kinase-mediated phosphorylation of the actin regulator vasodilator-stimulated phosphoprotein (VASP) at residue serine239. The function of this phosphorylation for smooth muscle cell (SMC) adhesion, spreading, matrix contraction, and invasion is not well understood. We reconstituted VASP deficient SMC with wild-type VASP (wt-VASP) or VASP mutants that mimic "locked" serine239 phosphorylation (S239D-VASP) or "blocked" serine239 phosphorylation (S239A-VASP). Collagen gel contraction was reduced in S239D-VASP compared to S239A-VASP and wt-VASP expressing cells and nitric oxide (NO) stimulation decreased gel contraction of wt-VASP reconstituted SMC. Invasion of collagen was enhanced in S239D-VASP and NO-stimulated wild-type SMCs compared to S239A-VASP expressing cells. Expression of S239D-VASP impaired SMC attachment to collagen, reduced the number of membrane protrusions, and caused cell rounding compared to expression of S239A-VASP. Treatment of wt-VASP reconstituted SMCs with NO exerted similar effects as expression of S239D-VASP. As unstimulated cells were spreading on collagen S239A-VASP and wt-VASP localized to actin fibers whereas S239D-VASP was enriched in the cytosol. NO interferes with SMC invasion and contraction of collagen matrices. This requires phosphorylation of VASP on serine239, which reduces VASP binding to actin fibers. These findings support the conclusion that VASP phosphorylation at serine239 regulates cytoskeleton remodeling.
KW - Animals
KW - Humans
KW - Mice
KW - Cell Adhesion/drug effects
KW - Actins/metabolism
KW - Cell Movement/drug effects
KW - Phosphorylation/drug effects
KW - Protein Transport/drug effects
KW - Collagen/metabolism
KW - Cell Adhesion Molecules/deficiency/metabolism
KW - Cell Shape/drug effects
KW - Cell Surface Extensions/drug effects/metabolism
KW - Gels
KW - Microfilament Proteins/deficiency/metabolism
KW - Mutant Proteins/metabolism
KW - Myocytes, Smooth Muscle/cytology/drug effects/metabolism
KW - Nitric Oxide/pharmacology
KW - Phosphoproteins/deficiency/metabolism
KW - Phosphoserine/metabolism
KW - Animals
KW - Humans
KW - Mice
KW - Cell Adhesion/drug effects
KW - Actins/metabolism
KW - Cell Movement/drug effects
KW - Phosphorylation/drug effects
KW - Protein Transport/drug effects
KW - Collagen/metabolism
KW - Cell Adhesion Molecules/deficiency/metabolism
KW - Cell Shape/drug effects
KW - Cell Surface Extensions/drug effects/metabolism
KW - Gels
KW - Microfilament Proteins/deficiency/metabolism
KW - Mutant Proteins/metabolism
KW - Myocytes, Smooth Muscle/cytology/drug effects/metabolism
KW - Nitric Oxide/pharmacology
KW - Phosphoproteins/deficiency/metabolism
KW - Phosphoserine/metabolism
M3 - SCORING: Journal article
VL - 222
SP - 230
EP - 237
JO - J CELL PHYSIOL
JF - J CELL PHYSIOL
SN - 0021-9541
IS - 1
M1 - 1
ER -
