Find Rap1 Products Interaction Network for Rap1 Rap1 Details

Related Pathways Synaptic Long Term Potentiation cAMP-mediated Signaling ERK/MAPK Signaling View All Pathways

Synonyms: AI848598, C21KG, EG668838, G-22K, KREV-1, MGC102329, RAP1, RAP1A, SMGP21

Rap1 Pathway

Rap family members (Rap1A, Rap1B, Rap2A, Rap2B, and Rap2C) are small Ras-like GTPases that regulate cell proliferation, differentiation, apoptosis (PDA activities) and adhesion mechanisms. Raps are regulated by specific RapGEF, RapGAP, and RapGDI molecules, and their location relative to specific upstream and downstream effector molecules. These factors integrate to provide specificity to Rap actions. They also mediate cross-talk among signaling pathways.

Rap1 (Ras-proximate-1) regulates PDA activities through interaction with two MAP3K effectors of the MEK/ERK MAP-kinase pathway, Raf-1 and B-Raf. Rap1 activates the MEK/ERK pathway via interaction with BRaf and inhibits MEK/ERK activity by binding Raf-1. As an inhibitor of the Raf-1 pathway Rap-GTPase is an antagonist of Ras-GTPase. Rap1 activity that regulates ERK activity through Raf-1 and B-Raf is associated primarily with the plasma membrane (PM) and it is regulated by GEFs represented by C3G (Crk SH3 domain Guanine nucleotide exchanger) and Smg GDS. The Rap1 ERK signaling pathway responds to Src kinases and cAMP via activation of PKA. Rap1 involved with ERK signaling is linked to cell receptors via adaptor and scaffold proteins such as c-Cbl and CrkL.

Rap1 regulates cell adhesion mechanisms through effector molecules such as the integrins and cadherins. RIAM (Rap1-GTP-interacting adaptor molecule) links Rap1 to integrin activation. The Rap1 regulation of cell adhesion processes involves a family of GEFs that are directly activated by cAMP: Epac 1(cAMP-GEFI) and Epac 2 (cAMP-GEFII). The activation of Rap1 involved with intergrin and cadherins activity is topologically regulated by the localized expression of Epacs and effectors of Epac activation.

Various GPCR receptor signals modulate the activity of Rap through trimeric G-protein subunits. For example, unactivated Galpha(o) stimulates Rap1-dependent ERK activation by sequestering Rap1GAP. Whereas Galpha(s) and Galpha(i) regulate the levels of cAMP through adenylyl cyclase activation and inhibition, respectively.