Reactome | cAMP activates EPAC1

cAMP activates EPAC1

Stable Identifier

R-HSA-381668

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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Each molecule of RAPGEF3 / EPAC1 binds 1 molecule of cAMP. EPAC1 binds cAMP less tightly than PKA binds cAMP so it is believed that EPAC1 binds cAMP after PKA is saturated. The binding of cAMP by EPAC1 activates the guanyl nucleotide exchange activity of EPAC1. EPAC1 also binds the SUR1 subunit of ATP-gated potassium channels (KATP channels) in beta cells so EPAC1 may participate in direct regulation of potassium transport.
EPAC1 also interacts with the calcium sensor Piccolo in a complex with Rim2 at the cell membrane. This may influence exocytosis of insulin.

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 Fujimoto, K, Shibasaki, T, Yokoi, N, Kashima, Y, Matsumoto, M, Sasaki, T, Tajima, N, Iwanaga, T, Seino, S	J Biol Chem	2002
15569269	Glucagon-like peptide-1: regulation of insulin secretion and therapeutic potential Gromada, J, Brock, B, Schmitz, O, Rorsman, P	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 Kang, G, Joseph, JW, Chepurny, OG, Monaco, M, Wheeler, MB, Bos, JL, Schwede, F, Genieser, HG, Holz, GG	J Biol Chem	2003
16973695	Cell physiology of cAMP sensor Epac Holz, GG, Kang, G, Harbeck, M, Roe, MW, Chepurny, OG	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 Kang, G, Chepurny, OG, Malester, B, Rindler, MJ, Rehmann, H, Bos, JL, Schwede, F, Coetzee, WA, Holz, GG	J Physiol	2006
11071853	Expression of cAMP-regulated guanine nucleotide exchange factors in pancreatic beta-cells Leech, CA, Holz, GG, Chepurny, O, Habener, JF	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 Kang, G, Leech, CA, Chepurny, OG, Coetzee, WA, Holz, GG	J Physiol	2008
17306374	Mechanisms of action of glucagon-like peptide 1 in the pancreas Doyle, ME, Egan, JM	Pharmacol Ther	2007