title: Interrelationship between protein phosphatase 1 and TGF-{beta} in regulating motility and cytoskeletal architecture of endothelial cells.
abstract: Motility of endothelial cells is a requirement for the vascularization of solid malignancies. While tumors have been shown to produce a host of angiogenic factors, including TGF-β, the mechanisms by which such factors regulate endothelial cell motility have not yet been defined. Thus, the role of the serine/threonine phosphatase PP-1 in regulating endothelial cell motility and cytoskeletal architecture was studied. The present study demonstrated that TGF-β stimulation of motility is dependent on PP-1. Likewise, TGF-β was shown to up-regulate paxillin expression through a process that was PP-1 dependent. The interplay between PP-1 and TGF-β was further observed by the induction of cell rounding and the loss of paxillin-actin co precipitations upon PP-1 inhibition and the compensation for these effects by TGF-β. Studies initiated to determine how PP-1 might regulate motility showed its role in maintaining cytoskeletal organization and its capacity to directly dephosphorylate the focal adhesion scaffolding protein paxillin. These studies suggest that the interplay between TGF-β and PP-1 regulates the motility of endothelial cells that is critical to the process of angiogenesis.
authors.affiliation: Research Service 151, Ralph H Johnson VA Medical Center, Charleston, South Carolina 29401, USA.
authors.forename: Jarrett E
authors.initials: JE
authors.lastname: Walsh
authors.forename: M Rita I
authors.initials: MR
authors.lastname: Young
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D017077:Culture Media, Conditioned; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D022001:Focal Adhesions / Q000187:drug effects; D005663:Furans / Q000494:pharmacology; D006801:Humans; D008055:Lipids / Q000494:pharmacology; D051379:Mice; D051419:Paxillin / Q000096:biosynthesis / Q000378:metabolism; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000199:Actins; D017077:Culture Media, Conditioned; D005663:Furans; D008055:Lipids; D051419:Paxillin; D016212:Transforming Growth Factor beta; C058744:tautomycetin; D054645:Protein Phosphatase 1