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Cell physiology of cAMP sensor Epac.

George G Holz1, Guoxin Kang, Mark Harbeck

  • 1Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016, USA. holzg01@popmail.med.nyu.edu

The Journal of Physiology
|September 16, 2006
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Summary

Exchange proteins activated directly by cyclic AMP (Epac) mediate crucial cellular functions independently of protein kinase A. Epac-selective cyclic AMP analogues reveal new roles in ion channel regulation and exocytosis.

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Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Biochemistry

Background:

  • Epac (exchange proteins activated directly by cyclic AMP) are cAMP-regulated guanine nucleotide exchange factors.
  • Epac mediate protein kinase A (PKA)-independent signal transduction pathways.
  • Epac activate Rap GTPase, influencing cell adhesion, barrier formation, and gap junctions.

Purpose of the Study:

  • To review novel PKA-independent cAMP signal transduction pathways mediated by Epac.
  • To highlight the role of Epac-selective cyclic AMP analogues (ESCAs) in uncovering new physiological processes.
  • To update on Epac's role in regulating ion channels, Ca(2+) signaling, transporters, and exocytosis.

Main Methods:

  • Utilized Epac-selective cyclic AMP analogues (ESCAs) like 8-pCPT-2'-O-Me-cAMP.
  • Investigated effects of ESCAs on ion channel function (Na(+), K(+), Ca(2+), Cl(-)).
  • Examined ESCAs' impact on intracellular Ca(2+) and Na(+)-H(+) transporter activity.
  • Studied ESCAs' actions on neurons, pancreatic beta cells, pituitary cells, and sperm.

Main Results:

  • ESCAs activate Epac1 and Epac2, but not PKA at low concentrations.
  • ESCAs alter ion channel function and intracellular Ca(2+) levels.
  • ESCAs modulate Na(+)-H(+) transporter activity.
  • ESCAs stimulate cAMP-dependent exocytosis in various cell types.

Conclusions:

  • Epac plays a significant role in cAMP-mediated cellular processes independent of PKA.
  • ESCAs are valuable tools for dissecting Epac-specific signaling.
  • Epac is crucial for regulating ion transport, Ca(2+) homeostasis, and exocytosis.