Reactome | cAMP activates EPAC2

cAMP activates EPAC2

Stable Identifier

R-HSA-381608

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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Each molecule of EPAC2 / RAPGEF4 binds 2 molecules of cAMP. EPAC2 binds cAMP less tightly than PKA binds cAMP so it is believed that EPAC2 binds cAMP after PKA is saturated. The binding of cAMP by EPAC2 activates the guanyl nucleotide exchange activity of EPAC2. EPAC2 also directly binds the SUR1 subunits of ATP-gated potassium channels (KATP channels) in beta cells so EPAC2 may regulate potassium transport.
EPAC2 interacts with the calcium sensor Piccolo in a complex with Rim2 at the cell membrane. This may influence exocytosis of insulin. EPAC2 also interacts with the ryanodine-sensitive calcium channel on the ER membrane and may cause release of calcium from the ER into the cytosol.

Literature References

PubMed ID	Title	Journal	Year
12401793	Piccolo, a Ca2+ sensor in pancreatic beta-cells. Involvement of cAMP-GEFII.Rim2.Piccolo complex in cAMP-dependent exocytosis Matsumoto, M, Yokoi, N, Tajima, N, Seino, S, Kashima, Y, Shibasaki, T, Iwanaga, T, Sasaki, T, Fujimoto, K	J Biol Chem	2002
15569269	Glucagon-like peptide-1: regulation of insulin secretion and therapeutic potential Brock, B, Gromada, J, Rorsman, P, Schmitz, O	Basic Clin Pharmacol Toxicol	2004
12496249	Epac-selective cAMP analog 8-pCPT-2'-O-Me-cAMP as a stimulus for Ca2+-induced Ca2+ release and exocytosis in pancreatic beta-cells Bos, JL, Monaco, M, Holz, GG, Chepurny, OG, Joseph, JW, Wheeler, MB, Schwede, F, Genieser, HG, Kang, G	J Biol Chem	2003
16973695	Cell physiology of cAMP sensor Epac Chepurny, OG, Harbeck, M, Holz, GG, Roe, MW, Kang, G	J Physiol	2006
16613879	cAMP sensor Epac as a determinant of ATP-sensitive potassium channel activity in human pancreatic beta cells and rat INS-1 cells Bos, JL, Malester, B, Holz, GG, Chepurny, OG, Rehmann, H, Rindler, MJ, Schwede, F, Kang, G, Coetzee, WA	J Physiol	2006
11071853	Expression of cAMP-regulated guanine nucleotide exchange factors in pancreatic beta-cells Holz, GG, Habener, JF, Leech, CA, Chepurny, O	Biochem Biophys Res Commun	2000
18202100	Role of the cAMP sensor Epac as a determinant of KATP channel ATP sensitivity in human pancreatic beta-cells and rat INS-1 cells Holz, GG, Chepurny, OG, Leech, CA, Kang, G, Coetzee, WA	J Physiol	2008
17306374	Mechanisms of action of glucagon-like peptide 1 in the pancreas Egan, JM, Doyle, ME	Pharmacol Ther	2007