Deficient R-smad/smad4 complex formation in fibroblasts growth-stimulated by TGF-beta 1.
Although most cell types are inhibited by TGF-beta 1 some mesenchymal cells are growth-stimulated by TGF-beta 1. Here, using two cell models, in which the normal untransformed cells (WI38 human embryo and NIH3T3 mouse fibroblasts) are stimulated to proliferate by TGF-beta 1 and their SV40 Large T-transformed counterparts are inhibited, we show that the two former cells are deficient in smad2-smad4 and smad3-smad4 complex formation, whereas these complexes are present in the two latter cells. In addition, endogenous smad4 levels in total cell extracts are lower in WI38 and NIH3T3 fibroblasts than in their Large T-expressing counterparts. In WI38 fibroblasts smad4 is, at best, inefficiently translocated to the nucleus. TGF-beta 1-mediated growth-stimulation of these normal fibroblasts does not appear to involve the presently known smads, but this situation is reversed in the Large T-transformed cells inhibited by TGF-beta 1.
Lawrence
David A
DA
Laboratoire de Radiobiologie et Etude du Génome, INRA/CEA, Domaine de Vilvert, 78352 Jouy-en-Josas, France. lawrence@dsvidf.cea.fr
D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D011233:Precipitin Tests; D013539:Simian virus 40 / Q000235:genetics; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D015534:Trans-Activators / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1