cAMP activates EPAC2

Stable Identifier
R-HSA-381608
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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Each molecule of Epac2 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 has also been shown to directly bind 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
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
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
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
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