title: Vasodilator-stimulated phosphoprotein regulates proliferation and growth inhibition by nitric oxide in vascular smooth muscle cells.
abstract: OBJECTIVE
  Vasodilator-stimulated phosphoprotein (VASP) was identified as a substrate for cGMP-dependent protein kinase (PKG) and cAMP-dependent protein kinase (PKA). It is preferentially phosphorylated at serine239 by PKG, whereas serine157 is a preferred phosphorylation site for PKA. In addition, serine157 is phosphorylated by PKC in response to serum. We have investigated the effects of VASP and VASP phosphorylation at serine157 and serine239 on smooth muscle cell (SMC) proliferation and nitric oxide (NO)-mediated growth inhibition.
  
  
  RESULTS
  Aortic SMCs derived from VASP-deficient mice were transduced with retroviral vectors encoding either wild-type VASP or VASP mutants (S157A-VASP and S239A-VASP), in which serine157 and serine239, respectively, were replaced by a nonphosphorylatable amino acid, alanine. Expression of wt-VASP and S239A-VASP significantly increased proliferation, whereas expression of S157A-VASP was inhibitory. Expression of S239A-VASP rendered SMCs less sensitive to growth inhibition by the NO donor, S-nitroso-n-acetylpenicillamine, when compared with cells expressing wt-VASP. Similar effects were observed in cultured rat SMCs in which wt-VASP, S157A-VASP, and S239A-VASP were expressed.
  
  
  CONCLUSIONS
  Our data suggest that VASP phosphorylation at serine157 is required for the growth-stimulatory effect of VASP in SMCs, whereas VASP phosphorylation at serine239 is involved in the growth inhibitory effects of NO on SMCs.
authors.affiliation: Department of Surgery, University of Washington, Seattle, WA 98195, USA. lihua@u.washington.edu
authors.forename: Lihua
authors.initials: L
authors.lastname: Chen
authors.forename: Günter
authors.initials: G
authors.lastname: Daum
authors.forename: Kanchan
authors.initials: K
authors.lastname: Chitaley
authors.forename: Scott A
authors.initials: SA
authors.lastname: Coats
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Bowen-Pope
authors.forename: Martin
authors.initials: M
authors.lastname: Eigenthaler
authors.forename: Naresh R
authors.initials: NR
authors.lastname: Thumati
authors.forename: Ulrich
authors.initials: U
authors.lastname: Walter
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Clowes
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001011:Aorta / Q000166:cytology; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003470:Culture Media / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004261:DNA Replication; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D005312:Fetal Blood; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D020125:Mutation, Missense; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism*; D017354:Point Mutation; D011499:Protein Processing, Post-Translational; D051381:Rats; D011916:Rats, Inbred F344; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013329:Structure-Activity Relationship; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D003470:Culture Media; D016895:Culture Media, Serum-Free; D008840:Microfilament Proteins; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D000098662:Vasodilator-Stimulated Phosphoprotein; D010768:Phosphoserine; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D003995:Dibutyryl Cyclic GMP; D006152:Cyclic GMP