title: Regulation of myosin light chain function by BMP signaling controls actin cytoskeleton remodeling.
abstract: OBJECTIVE
  Actin cytoskeleton dynamics support and coordinate signaling events that control cell proliferation, differentiation and migration. Growth factors provide essential signals that act on multi-protein complexes that regulate actin assembly with myosin. We previously analyzed the action of the transforming growth factor β (TGF-β) and now extend our studies to the bone morphogenetic protein (BMP) 7, an important regulator of stem cell function and bone differentiation.
  
  
  METHODS
  Using a well-established cell model of actin dynamics, Swiss3T3 fibroblasts, we applied cell biological and biochemical approaches to monitor the pathway that links the BMP-7 receptors to the acto-myosin complex.
  
  
  RESULTS
  We demonstrate that BMP-7 induces actin and focal adhesion remodeling in starved fibroblasts as potently as TGF-β. BMP-7 mediates changes of actin dynamics via the kinase ROCK1 and induces rapid activation of RhoA and RhoB with concomitant inactivation of Cdc42. These molecular events correlate well with induction of phosphorylation on Ser19 of the myosin light chain, but not with LIMK1 kinase activation. Depletion of endogenous myosin light chain inhibits actin remodeling induced by BMP-7. This novel pathway regulates fibroblast migration without affecting cell proliferation.
  
  
  CONCLUSIONS
  We establish a BMP-Rho-ROCK1 pathway, which targets myosin light chain to control actin remodeling in fibroblasts.
authors.affiliation: Department of Biochemistry, University of Crete Medical School, Heraklion, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Konstantinidis
authors.forename: Aristidis
authors.initials: A
authors.lastname: Moustakas
authors.forename: Christos
authors.initials: C
authors.lastname: Stournaras
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D054461:Lim Kinases / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D018994:Myosin Light Chains / Q000378:metabolism*; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D015398:Signal Transduction; D041701:Swiss 3T3 Cells; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D020743:rhoB GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D055419:Bone Morphogenetic Protein 7; D018994:Myosin Light Chains; D016212:Transforming Growth Factor beta; D054461:Lim Kinases; C515893:Limk1 protein, mouse; C515854:Rock1 protein, mouse; D054460:rho-Associated Kinases; D020764:cdc42 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein; D020743:rhoB GTP-Binding Protein