RASGRP, A RAS GUANYL NUCLEOTIDE-RELEASING PROTEIN WITH CALCIUM-BINDING AND DIACYLGLYCEROL-BINDING MOTIFS

RasGRP, a guanyl nucleotide-releasing protein for the small guanosine triphosphatase Ras, was characterized. Besides the catalytic domain, R asGRP has an atypical pair of ''EF hands'' that bind calcium and a dia cylglycerol (DAG)-binding domain. RasGRP activated Ras and caused tran sformation in fibroblasts. A DAG analog caused sustained activation of Ras-Erk signaling and changes in cell morphology. Signaling was assoc iated with partitioning of RasGRP protein into the membrane fraction. Sustained ligand-induced signaling and membrane partitioning were abse nt when the DAG-binding domain was deleted. RasGRP is expressed in the nervous system, where it may couple changes in DAG and possibly calci um concentrations to Ras activation.