Plays a crucial role in coupling NGF stimulation to the activation of both EPHB2 and MAPK14 signaling pathways and in NGF-dependent neuronal differentiation.
Neuronal activity dramatically increases the concentration of cytosolic Ca2+, which then serves as a second messenger to direct diverse cellular responses. Calmodulin is a primary mediator of Ca2+ signals in the nervous system. Ric, a protein related to the Ras subfamily of small GTPases, has the ability to bind calmodulin. In addition, two Ras-like human proteins, Rin and Rit (Ric-related gene expressed in many tissues), which are 71% and 66% identical to RIC respectively, share related G2 domains with Ric. While most members of the Ras subfamily are plasma membrane-associated and generally require a C-terminal isoprenyl group to bind to the plasma membrane, Rit and Rin lack the recognition signal for C-terminal prenylation. Transiently expressed Rit and Rin are plasma membrane-localized because both proteins contain a C-terminal cluster of basic amino acids, which provides a mechanism for membrane association. Rin binds calmodulin through a C-terminal binding motif. Rit and Ric are widely expressed, whereas expression of Rin is restricted to the neuron system. In conclusion, Rit and Rin define a novel subfamily of Ras-related proteins