A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia.

摘要: Ras proteins, key regulators of growth, differentiation, and malignant transformation, recently have been implicated in synaptic function region-specific learning memory functions the brain. Rap members small G protein superfamily, can inhibit signaling through Ras/Raf-1/mitogen-activated (MAP) kinase pathway or, B-Raf, activate MAP kinase. proteins both be activated guanine nucleotide exchange factors (GEFs). Many GEFs, but to date only one GEF, identified. We now report cloning a brain-enriched gene, CalDAG-GEFI, which has substrate specificity for Rap1A, dual binding domains calcium (Ca2+) diacylglycerol (DAG), enriched expression brain basal ganglia pathways their axon-terminal regions. Expression CalDAG-GEFI activates Rap1A inhibits Ras-dependent activation Erk/MAP cascade 293T cells. Ca2+ ionophore phorbol ester strongly additively enhance this activation. By contrast, CalDAG-GEFII, second CalDAG-GEF family member that we cloned found identical RasGRP [Ebinu, J. O., Bottorff, D. A., Chan, E. Y. W., Stang, S. L., Dunn, R. & Stone, C. (1998) Science 280, 1082–1088], exhibits different pattern fails H-Ras, R-Ras, under DAG modulation. propose critical neuronal determining relative Rap1 induced by mobilization. The CalDAG-GEFII hematopoietic organs suggests such control may broad significance Ras/Rap regulation normal states.