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Updated: Aug 9, 2026

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
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TGF-beta 1 induces phosphorylation of the cyclic AMP responsive element binding protein in ML-CCl64 cells

I M Kramer1, I Koornneef, S W de Laat

  • 1Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht, The Netherlands.

The EMBO Journal
|May 1, 1991
PubMed

Insights

Transforming growth factor-beta 1 (TGF-beta 1) rapidly phosphorylates cyclic AMP responsive element binding protein (CREB) in mink lung cells. This modification enhances CREB binding to the collagenase TRE, suggesting a novel TGF-beta signaling pathway.

Area of Science:

  • Cellular signaling
  • Molecular biology
  • Cancer research

Background:

  • Transforming growth factor-beta (TGF-beta) is a key regulator of cell growth and differentiation.
  • TGF-beta mediates its effects via cell surface receptors, but downstream signaling pathways remain incompletely understood.
  • Understanding TGF-beta signaling is crucial for developing targeted therapies for diseases like cancer.

Purpose of the Study:

  • To investigate the signal transduction pathways activated by TGF-beta 1.
  • To identify specific proteins and mechanisms involved in TGF-beta 1-mediated cellular responses.
  • To elucidate the role of CREB phosphorylation in TGF-beta 1 signaling.

Main Methods:

  • Treatment of mink lung CCl64 cells with TGF-beta 1.
  • Analysis of cyclic AMP responsive element binding protein (CREB) phosphorylation.
  • Assessment of CREB binding to the collagenase TPA responsive element (TRE).

Main Results:

  • TGF-beta 1 rapidly induced CREB phosphorylation in CCl64 cells.
  • CREB phosphorylation was independent of cAMP-dependent protein kinase.
  • TGF-beta 1 treatment increased the binding of CREB to the TRE, likely as a heterodimer.

Conclusions:

  • TGF-beta 1 activates a novel signaling pathway involving CREB phosphorylation.
  • Enhanced CREB-TRE binding may mediate TGF-beta 1-induced transcriptional activation.
  • This finding provides new insights into TGF-beta 1's role in regulating gene expression.

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