RalGEF2, a pleckstrin homology domain containing guanine nucleotide exchange factor for Ral

Ral is a ubiquitously expressed Ras-like small GTPase. Several guanine nucl eotide exchange factors for Ral have been identified, including members of the RalGDS family, which exhibit a Pas binding domain and are regulated by binding to RasGTP. Here we describe a novel type of RalGEF, RalGEF2. This g uanine nucleotide exchange factor has a characteristic Cdc25-like catalytic domain at the N terminus and a pleckstrin homology (PH) domain at the C te rminus. RalGEF2 is able to activate Ral both in vivo and in vitro. Deletion of the PH domain results in an increased cytoplasmic localization of the p rotein and a corresponding reduction in activity in vivo, suggesting that t he PH domain functions as a membrane anchor necessary for optimal activity in vivo.