Characterization of GFR, a novel guanine nucleotide exchange factor for Rap1

Three groups of Rap1-specific guanine nucleotide exchange factors including C3G, CalDAG-GEFI, and Epac/cAMP-GEFI/II have been identified to date. In the present study, we report a new Rap1 guanine nucleotide exchange factor which we have named GFR (guanine nucleotide exchange factor for Rap1). GFR shows close sequence similarity to EPAC/cAMP-GEFI/II although GFR lacks a cAMP binding domain and contains a nuclear localization signal. We demonstrated that GFR can activate Rap1 but not H-Ras in 293T cells and that the cdc25 domain of GFR is required for the activation of Rap1. Northern blot analysis suggested that GFR mRNA is strongly expressed in the brain. In transfected HeLa cells, GFR has been found to be localized in the nuclei.