Activation of Ras proteins by Ras guanine nucleotide releasing protein family members.

Ras guanine nucleotide releasing proteins (RasGRPs) function as guanine nucleotide exchange factors for Ras proteins. Thus, RasGRPs are direct activators of Ras proteins and contribute an important role in various cell-signaling pathways that are regulated by the activation state of Ras proteins. RasGRPs are regulated by the second messengers diacylglycerol and intracellular calcium and are also known as CalDAG-GEFs or calcium and diacylglycerol-regulated guanine nucleotide exchange factors. RasGRPs couple signaling events that generate these second messengers in the cell into activation of signaling pathways that are regulated by Ras. RasGRPs, therefore, increase the repertoire of extracellular stimuli that lead to activation of Ras. Analyzing the regulation of RasGRP activity should continue to play an important role in understanding the mechanisms by which signal transduction pathways use RasGRP proteins to activate Ras proteins in cells.