Rap1B regulation pathway
RAP1B member of RAS oncogene family ( Rap-1B ) is a member of the Ras-like small GTPases family. It is activated by many extracellular stimuli and is strongly implicated in the control of integrin-mediated cell adhesion , , , .
Rap-1B is posttranslationally modified by geranylgeranylation of cysteine 181 residue, catalyzed by Geranylgeranyltransferase type I ( GGTase-I ) . Geranylgeranylated Rap-1B undergoes RCE1 homolog prenyl protein peptidase ( CAAX prenyl protease 2 )-dependent processing .
Activity of Rap-1B is mainly regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). GEFs and GAPs promote GTP (active) and GDP (inactive) state of Rap-1B, respectively .
RAP1 GTP-GDP dissociation stimulator 1 ( RAP1GDS1 ) and Rap guanine nucleotide exchange factor 1 ( C3G ) are known GEFs for Rap-1B . Kinesin-associated protein 3 ( KAP3 ) binds to RAP1GDS1 and stimulates its activity . C3G activity is stimulated by Growth factor receptor-bound protein 2 ( GRB2 ) . Activated RAP1GDS1 and C3G are capable to stimulate GDP/GDP exchange and to activate Rap-1B , .
Protein kinase cAMP-dependent catalytic ( PKA-cat (cAMP-dependent) ) stimulated by cAMP is capable to phosphorylate and activate Rap-1B and this stimulates Rap-1B association with ATPase Ca ++ transporting ubiquitous ( Ca-ATPase3 ) , , .