Epac and PKA: a tale of two intracellular cAMP receptors

Authors

  • Xiaodong Cheng,

    Corresponding author
    1. Department of Pharmacology and Toxicology, Sealy Center for Cancer Cell Biology and Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, Texas 77555-1031, USA
      *Corresponding author: Tel, 1-409-772-9656; Fax, 1-409-772-9642; E-mail, xcheng@utmb.edu
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  • Zhenyu Ji,

    1. Department of Pharmacology and Toxicology, Sealy Center for Cancer Cell Biology and Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, Texas 77555-1031, USA
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  • Tamara Tsalkova,

    1. Department of Pharmacology and Toxicology, Sealy Center for Cancer Cell Biology and Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, Texas 77555-1031, USA
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  • Fang Mei

    1. Department of Pharmacology and Toxicology, Sealy Center for Cancer Cell Biology and Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, Texas 77555-1031, USA
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  • This work was supported by grants from the National Institutes of Health (No. GM061770) and the American Heart Association (No. 0755049Y)

*Corresponding author: Tel, 1-409-772-9656; Fax, 1-409-772-9642; E-mail, xcheng@utmb.edu

Abstract

cAMP-mediated signaling pathways regulate a multitude of important biological processes under both physiological and pathological conditions, including diabetes, heart failure and cancer. In eukaryotic cells, the effects of cAMP are mediated by two ubiquitously expressed intracellular cAMP receptors, the classic protein kinase A (PKA)/cAMP-dependent protein kinase and the recently discovered exchange protein directly activated by cAMP (Epac)/cAMP-regulated guanine nucleotide exchange factors. Like PKA, Epac contains an evolutionally conserved cAMP binding domain that acts as a molecular switch for sensing intracellular second messenger cAMP levels to control diverse biological functions. The existence of two families of cAMP effectors provides a mechanism for a more precise and integrated control of the cAMP signaling pathways in a spatial and temporal manner. Depending upon the specific cellular environments as well as their relative abundance, distribution and localization, Epac and PKA may act independently, converge synergistically or oppose each other in regulating a specific cellular function.

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