TGF-β signaling

A tale of two responses

Rod A. Rahimi, Edward B Leof

Research output: Contribution to journalArticle

284 Citations (Scopus)

Abstract

Transforming growth factor-β (TGF-β) regulates a wide variety of cellular processes including cell growth, apoptosis, differentiation, migration, and extracellular matrix production among others. The canonical signaling pathway induced by the TGF-β receptor complex involves the phosphorylation of Smad proteins which upon activation accumulate in the nucleus and regulate transcription. Interestingly, the cellular response to TGF-β can be extremely variable depending on the cell type and stimulation context. TGF-β causes epithelial cells to undergo growth arrest and apoptosis, responses which are critical to suppressing carcinogenesis, whereas it can also induce epithelial-mesenchymal transition and mediate fibroblast activation, responses implicated in promoting carcinogenesis and fibrotic diseases. However, TGF-β induces all these responses via the same receptor complex and Smad proteins. To address this apparent paradox, during the last few years a number of additional signaling pathways have been identified which potentially regulate the different cellular responses to TGF-β. The identification of these signaling pathways has shed light onto the mechanisms whereby Smad and non-Smad pathways collaborate to induce a particular cellular phenotype. In this article, we review TGF-β signaling in epithelial cells and fibroblasts with a focus on understanding the mechanisms of TGF-β versatility.

Original languageEnglish (US)
Pages (from-to)593-608
Number of pages16
JournalJournal of Cellular Biochemistry
Volume102
Issue number3
DOIs
StatePublished - Oct 15 2007

Fingerprint

Transforming Growth Factors
Smad Proteins
Fibroblasts
Carcinogenesis
Cell Growth Processes
Epithelial Cells
Chemical activation
Apoptosis
Phosphorylation
Epithelial-Mesenchymal Transition
Growth Factor Receptors
Cell growth
Transcription
Extracellular Matrix
Phenotype
Growth

Keywords

  • Apoptosis
  • EMT
  • Epithelia
  • Fibroblasts
  • Growth arrest
  • Non-Smad
  • Signaling
  • Smad
  • TGF-β

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

TGF-β signaling : A tale of two responses. / Rahimi, Rod A.; Leof, Edward B.

In: Journal of Cellular Biochemistry, Vol. 102, No. 3, 15.10.2007, p. 593-608.

Research output: Contribution to journalArticle

Rahimi, Rod A. ; Leof, Edward B. / TGF-β signaling : A tale of two responses. In: Journal of Cellular Biochemistry. 2007 ; Vol. 102, No. 3. pp. 593-608.
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