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Updated: Aug 18, 2026

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
07:41

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

Published on: February 20, 2018

Activating transcription factor-1 is a specific antagonist of the cyclic adenosine 3'.5'-monophosphate (cAMP)

M J Ellis1, A C Lindon, K J Flint

  • 1Gene Regulation Laboratories, Imperial Cancer Research Fund, London, United Kingdom.

Molecular Endocrinology (Baltimore, Md.)
|February 1, 1995
PubMed

Insights

Cellular response to somatostatin depends on CREB-1 protein. Homodimeric CREB-1 enables cAMP response, while heterodimers with ATF-1 inhibit it, explaining functional variability.

Area of Science:

  • Molecular biology
  • Cellular signaling
  • Gene regulation

Background:

  • The somatostatin cAMP response element (CRE) function varies across cell lines.
  • CREB-1 protein mediates transactivation via protein kinase-A in response to cAMP.
  • Both cAMP-responsive and non-responsive cells possess CREB-1 that binds to somatostatin CRE.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying the variable function of the somatostatin CRE.
  • To determine the role of CREB-1 protein forms in mediating cAMP responses.

Main Methods:

  • Analysis of CREB-1 protein forms (homodimers vs. heterodimers with ATF-1) in different cell lines.
  • Transfection experiments to assess the functional impact of CREB-1/ATF-1 interactions.

Main Results:

  • All tested cells contain CREB-1 capable of binding to the somatostatin CRE.
  • Responsive cells exhibit a higher proportion of CREB-1 homodimers compared to non-responsive cells.
  • Activating transcription factor-1 (ATF-1) antagonizes CREB-1-mediated activation.

Conclusions:

  • The formation of CREB-1 homodimers is crucial for mediating a cAMP response.
  • Heterodimerization of CREB-1 with ATF-1 down-regulates its ability to mediate cAMP responses.
  • Differential CREB-1/ATF-1 heterodimerization explains the variability in somatostatin CRE function across cell types.

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