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.
Huibin Yang, J. Biol. Chem., Apr 2003; 278: 13278 - 13285.
Huibin Yang, Mol. Biol. Cell, May 2006; 17: 2177 - 2189.
Raymond R. Mattingly, J. Biol. Chem., Dec 1999; 274: 37379.
Tie-Nian Zhu, J. Biol. Chem., May 2007; 282: 14816 - 14826.