RasGRP, a Ras Guanyl Nucleotide- Releasing Protein with Calcium- and Diacylglycerol-Binding Motifs

TLDR

RasGRP is a Ras guanyl nucleotide–releasing protein that contains EF‑hand calcium‑binding motifs and a diacylglycerol‑binding domain, and is expressed in the nervous system where it may couple DAG and calcium signals to Ras activation. RasGRP activates Ras, induces fibroblast transformation, and a DAG analog sustains Ras–Erk signaling and morphological changes through membrane partitioning, a process that requires the DAG‑binding domain.

Abstract

RasGRP, a guanyl nucleotide–releasing protein for the small guanosine triphosphatase Ras, was characterized. Besides the catalytic domain, RasGRP has an atypical pair of “EF hands” that bind calcium and a diacylglycerol (DAG)-binding domain. RasGRP activated Ras and caused transformation in fibroblasts. A DAG analog caused sustained activation of Ras-Erk signaling and changes in cell morphology. Signaling was associated with partitioning of RasGRP protein into the membrane fraction. Sustained ligand-induced signaling and membrane partitioning were absent when the DAG-binding domain was deleted. RasGRP is expressed in the nervous system, where it may couple changes in DAG and possibly calcium concentrations to Ras activation.