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- Title
Epac signaling pathway involves STEF, a guanine nucleotide exchange factor for Rac, to regulate APP processing
- Authors
Zaldua, Natalia; Gastineau, Monique; Hoshino, Mikio; Lezoualc’h, Frank; Zugaza, José L.
- Abstract
Abstract: 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.
- Subjects
AMYLOID beta-protein precursor; NUCLEOTIDES; GLYCOPROTEINS; ALZHEIMER'S disease
- Publication
FEBS Letters, 2007, Vol 581, Issue 30, p5814
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2007.11.053