Three groups of Rap1-specific guanine nucleotide exchange factors including
C3G, CalDAG-GEFI, and Epac/cAMP-GEFI/II have been identified to date. In t
he present study, me report a nem Rap1 guanine nucleotide exchange factor w
hich me have named GFR (guanine nucleotide exchange factor for Rap1), GFR s
hows close sequence similarity to EPAC/ cAMP-GEFI/II although GFR lacks a c
AMP binding domain and contains a nuclear localization signal. We demonstra
ted that GFR can activate Rap1 but not H-Ras in 293T cells and that the cdc
25 domain of GFR is required for the activation of Rap1, Northern blot anal
ysis suggested that GFR mRNA is strongly expressed in the brain. In transfe
cted HeLa cells, GFR has been found to be localized in the nuclei. (C) 1999
Federation of European Biochemical Societies.