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.

• Publication year

  1993

• Venue

  Journal of Biological Chemistry

• Publication date

  1993-09-15

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/s0021-9258(19)36591-3PMID 8366123
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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