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Updated: Aug 19, 2026

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
07:49

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

Biphasic role of TGF-beta1 in signal transduction and crosstalk

Charles E Wenner1, Shaochun Yan

  • 1Department of Cell and Molecular Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York 14263, USA.

Journal of Cellular Physiology
|May 27, 2003
PubMed

Insights

Transforming growth factor-beta1 (TGF-β1) can both activate and delay cell cycle progression in mouse embryonic fibroblasts. This study investigates TGF-β1 signaling pathways, revealing a role for PKA-Raf-1 interaction in delaying EGF-induced cell cycle activation.

Area of Science:

  • Cellular and Molecular Biology
  • Signal Transduction Pathways
  • Cell Cycle Regulation

Background:

  • Transforming growth factor-beta1 (TGF-β1) exhibits dual effects on cell cycle kinetics, inducing both activation and delay.
  • Understanding the molecular mechanisms underlying TGF-β1's opposing effects on cell proliferation is crucial for deciphering its role in mesenchymal cells.

Purpose of the Study:

  • To investigate the early signal transduction pathways activated by TGF-β1 in the presence and absence of epidermal growth factor (EGF).
  • To elucidate the molecular basis for TGF-β1's differential modulation of cell cycle progression, specifically its delay of EGF-induced proliferation.

Main Methods:

  • Analysis of early TGF-β1 and EGF signaling events in mouse embryonic fibroblasts.
  • Investigation of protein kinase A (PKA) catalytic subunit association with Raf-1.
  • Examination of Rho-like GTPase activity and its potential involvement in TGF-β1 signaling.

Main Results:

  • TGF-β1 downregulates p27(Kip1), promoting cell cycle activation, but also delays EGF-induced cell cycle progression.
  • TGF-β1 rapidly associates catalytic subunits of PKA with Raf-1 in G1-arrested fibroblasts, suggesting a role in delaying EGF responses.
  • A model for TGF-β1-induced translocation of Raf-1 to the plasma membrane is proposed, potentially involving Rho proteins.

Conclusions:

  • TGF-β1 modulates mitogen-induced cell proliferation in mesenchymal cells through complex post-receptor signaling.
  • Cross-talk between TGF-β1, PKA-mediated pathways, and potentially Rho proteins is critical for regulating cell cycle kinetics.
  • Inhibition of early EGF-induced p42/p44 mitogen-activated protein kinase (MAPK) by TGF-β1 likely occurs at the c-Raf locus.

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