cAMP activates EPAC2

Stable Identifier
Reaction [transition]
Homo sapiens
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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
Catalyst Activity

cAMP binding activity of RAPGEF4 [plasma membrane]

Orthologous Events
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