Open AccessExchange protein activated by cAMP (Epac) mediates cAMP activation of p38 MAPK and modulation of Ca 2+ -dependent K + channels in cerebellar neurons
Author(s) -
Jeanne Ster,
Frédéric de Bock,
Nathalie C. Guérineau,
Andrea Janossy,
Stéphanie Barrère-Lemaire,
Johannes L. Bos,
Joël Bockaert,
Laurent Fagni
Publication year - 2007
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0611031104
Subject(s) - guanine nucleotide exchange factor , protein kinase a , g protein , hyperpolarization (physics) , microbiology and biotechnology , gtpase , mapk/erk pathway , chemistry , adenylate kinase , signal transduction , biology , biophysics , kinase , biochemistry , receptor , nuclear magnetic resonance spectroscopy , organic chemistry
The exchange factor directly activated by cAMP (Epac) is a newly discovered direct target for cAMP and a guanine-nucleotide exchange factor for the small GTPase Rap. Little is known about the neuronal functions of Epac. Here we show that activation of Epac by specific cAMP analogs or by the pituitary adenylate cyclase-activating polypeptide induces a potent activation of the Ca2+ -sensitive big K+ channel, slight membrane hyperpolarization, and increased after-hyperpolarization in cultured cerebellar granule cells. These effects involve activation of Rap and p38 MAPK, which mobilizes intracellular Ca2+ stores. These findings reveal a cAMP Epac-dependent and protein kinase A-independent signaling cascade that controls neuronal excitability.