Signaling events initiated by transforming growth factor-beta 1 that require Gi alpha 1.
Transforming growth factor-beta 1 (TGF-beta 1) initiates a series of signaling events leading to diverse cell type-specific effects on proliferation and morphology. The multiple effects of TGF-beta 1 are not due to selective expression of receptor subtypes, but rather probably reflect cell-specific expression of downstream components of the particular signaling system. To address this possibility and to identify specific signaling pathways activated by TGF-beta 1, we attempted to restore cell responsiveness to the cytokine by introducing various intracellular signal transducers in NIH-3T3 fibroblasts, a cell line that is minimally responsive to TGF-beta 1. In NIH-3T3 fibroblasts stably transfected with Gi alpha 1 cDNA, TGF-beta 1 induced a reversible morphological transformation that was identical to the effect of this cytokine in indicator cells such as AKR-2B fibroblasts. Gi alpha 1 transfectants also exhibited mitogenic hyperresponsiveness to TGF-beta 1. TGF-beta 1 does not elicit these responses in control nontransfected fibroblasts or cells transfected with the guanine nucleotide-binding protein Go alpha 1. The response to TGF-beta 1 in Gi alpha 1 transfectants is blocked by pertussis toxin and is lost in Gi alpha 1 transfectants that have spontaneously reverted and no longer express Gi alpha 1. These data indicate that the expression of the guanine nucleotide-binding protein Gi alpha 1, normally absent in these cells, confers cell sensitivity to TGF-beta 1.
Kataoka
R
R
Department of Pharmacology, Medical University of South Carolina, Charleston 29425-2251.
Sherlock
J
J
Lanier
S M
SM
D016475:3T3 Cells; D000818:Animals; D000077214:Becaplermin; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D015183:Restriction Mapping; D015398:Signal Transduction / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D000077214:Becaplermin; D008668:Metallothionein; D019204:GTP-Binding Proteins; D013936:Thymidine