Epac: effectors and biological functions.
Epac1 (also known as cAMP-GEF-I) and Epac2 (also known as cAMP-GEF-II) are cyclic AMP-activated guanine nucleotide exchange factors for Ras-like GTPases. Since their discovery about 10 years ago, it is now accepted that Epac proteins are novel cAMP sensors that regulate several pivotal cellular processes, including calcium handling, cell proliferation, cell survival, cell differentiation, cell polarization, cell-cell adhesion events, gene transcription, secretion, ion transport, and neuronal signaling. Recent studies even indicated that Epac proteins might play a role in the regulation of inflammation and the development of cardiac hypertrophy. Meanwhile, a plethora of diverse effectors of Epac proteins have been assigned, such as Ras and Rho GTPases, phospholiase C-epsilon, phospholipase D, mitogen-activated protein kinases, protein kinase B/Akt, ion channels, secretory-granule associated proteins and regulators of the actin-microtubule network, the latter probably involved in the spatiotemporal dynamics of Epac-related signaling. This review highlights multi-faceted effectors and diverse biological functions driven by Epac proteins that might explain certain controversial signaling properties of cAMP.
Roscioni
Sara S
SS
Department of Molecular Pharmacology, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Elzinga
Carolina R S
CR
Schmidt
Martina
M
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D002468:Cell Physiological Phenomena; D000242:Cyclic AMP / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000502:physiology; D008870:Microtubules / Q000502:physiology; D015398:Signal Transduction
D020662:Guanine Nucleotide Exchange Factors; D007473:Ion Channels; C116122:RAPGEF3 protein, human; C442864:RAPGEF4 protein, human; D000242:Cyclic AMP