 identified cAMP-GEFI and cAMP-GEFII as novel genes enriched in brain using a differential display protocol and by screening clones with cAMP-binding motif.De Rooij and colleagues performed a database search for proteins with sequence homology to both GEFs for Ras and Rap1 and to cAMP-binding sites, which led to the identification and subsequent cloning of "RAPGEF3" gene.The discovery of EPAC family cAMP sensors suggests that the complexity and possible readouts of cAMP signaling are much more elaborate than previously envisioned.