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Epac signaling pathway involves STEF, a guanine nucleotide exchange factor for Rac, to regulate APP processing
Author(s) -
Zaldua Natalia,
Gastineau Monique,
Hoshino Mikio,
Lezoualc'h Frank,
Zugaza José L.
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.11.053
Subject(s) - guanine nucleotide exchange factor , rap1 , crosstalk , microbiology and biotechnology , signal transduction , secretion , rac1 , guanine , chemistry , cleavage (geology) , intracellular , nucleotide , biology , biochemistry , gene , physics , optics , paleontology , fracture (geology)
The amyloid precursor protein (APP) is a key protein involved in the development of Alzheimer's disease. We previously identified a signal transduction secretory pathway in which the small G protein Rac sets downstream of the cAMP/Epac/Rap1 signalling cascade regulating the α cleavage of APP [Maillet, M. et al. (2003) Crosstalk between Rap and Rac regulates secretion of sAPPα. Nat. Cell Biol. 5, 633–639]. We now report that Rap1 can physically and specifically associate with the guanine nucleotide exchange factor (GEF) STEF through its TSS region. A deleted TSS domain of STEF cells fails to activate Rac1 and dramatically decreases secretion of the non‐amyloidogenic soluble form of APP (sAPPα) induced by the cAMP‐binding protein Epac. Altogether, our data show that upon Epac activation, Rap1 recruits STEF through its TSS region and activates Rac1, which mediates APP processing.