Ras activity is regulated by GAP (GTPase activating proteins) and GEFs (guanine nucleotide exchange factors). Ras-GRF1 (also known as CDC25Mm) is neuronal RasGEF and is regulated by heterotrimeric G proteins and calcium influx . Binding to calmodulin and phosphorylation stimulate Ras-GRF1 activity. Multiple PKA phosphorylation sites on Ras-GRF have been identified. Phosphorylation on the two major sites, Ser54 and Ser822, inhibits Ras-GRF activity. Carbachol (a muscarinic agonist)-induced phosphorylation on Ser916 is essential but not sufficient for maximal Ras-GRF activity.