title: Coupling of TGF-beta-induced mitogenesis to G-protein activation in AKR-2B cells.
abstract: We have investigated the signal transduction mechanisms by which TGF-beta stimulates proliferation of AKR-2B murine fibroblasts. Enhanced incorporation of [3H]-thymidine into TGF-beta challenged cells was inhibited in a dose-dependent manner by pertussis toxin. EGF stimulated DNA synthesis was unaffected. Parallel biochemical analysis of pertussis toxin-challenged cells revealed that TGF-beta-induced inhibition of DNA synthesis was associated with ADP-ribosylation of a 41 kDa membrane component and a concomitant decrease in TGF-beta stimulated GTPase activity. These data, along with the observation that Gpp(NH)p decreases the affinity of the TGF-beta receptor for its ligand, strongly suggest that a GTP-binding protein is involved in TGF-beta-induced mitogenesis in AKR-2B cells.
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D051379:Mice; D010455:Peptides / Q000494:pharmacology*; D037342:Pertussis Toxin; D015291:Transforming Growth Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D010455:Peptides; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D006165:Guanylyl Imidodiphosphate; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D037342:Pertussis Toxin; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins