Abl regulates smooth muscle cell proliferation by modulating actin dynamics and ERK1/2 activation

Am J Physiol Cell Physiol. 2012 Apr 1;302(7):C1026-34. doi: 10.1152/ajpcell.00373.2011. Epub 2012 Feb 1.


Abl is a nonreceptor tyrosine kinase that has a role in regulating migration and adhesion of nonmuscle cells as well as smooth muscle contraction. The role of Abl in smooth muscle cell proliferation has not been investigated. In this study, treatment with endothelin-1 (ET-1) and platelet-derived growth factor (PDGF) increased Abl phosphorylation at Tyr(412) (an indication of Abl activation) in vascular smooth muscle cells. To assess the role of Abl in smooth muscle cell proliferation, we generated stable Abl knockdown cells by using lentivirus-mediated RNA interference. ET-1- and PDGF-induced cell proliferation was attenuated in Abl knockdown cells compared with cells expressing control shRNA and uninfected cells. Abl silencing also arrested cell cycle progression from G(0)/G(1) to S phase. Furthermore, activation of smooth muscle cells with ET-1 and PDGF induced phosphorylation of ERK1/2 and Akt. Abl knockdown attenuated ERK1/2 phosphorylation in smooth muscle cells stimulated with ET-1 and PDGF. However, Akt phosphorylation upon stimulation with ET-1 and PDGF was not reduced. Because Abl is known to regulate actin polymerization in smooth muscle, we also evaluated the effects of inhibition of actin polymerization on phosphorylation of ERK1/2. Pretreatment with the actin polymerization inhibitor latrunculin-A also blocked ERK1/2 phosphorylation during activation with ET-1 and PDGF. The results suggest that Abl may regulate smooth muscle cell proliferation by modulating actin dynamics and ERK1/2 phosphorylation during mitogenic activation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actins / metabolism*
  • Animals
  • Aorta / drug effects
  • Aorta / metabolism
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Growth Processes / drug effects
  • Cell Growth Processes / physiology
  • Cells, Cultured
  • Endothelin-1 / genetics
  • Endothelin-1 / metabolism
  • Enzyme Activation
  • Gene Knockdown Techniques / methods
  • Gene Silencing / drug effects
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / genetics
  • MAP Kinase Signaling System / physiology*
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism*
  • Oncogene Proteins v-abl / genetics
  • Oncogene Proteins v-abl / metabolism*
  • Phosphorylation / drug effects
  • Platelet-Derived Growth Factor / genetics
  • Platelet-Derived Growth Factor / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Thiazolidines / pharmacology


  • Actins
  • Bridged Bicyclo Compounds, Heterocyclic
  • Endothelin-1
  • Oncogene Proteins v-abl
  • Platelet-Derived Growth Factor
  • Thiazolidines
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • latrunculin A