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Lead Time
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Usage
For Research Use Only. Not for use in diagnostic or therapeutic procedures.
Functions as a guanine nucleotide exchange factor (GEF), which activates Rap and Ras family of small GTPases by exchanging bound GDP for free GTP in a cAMP-dependent manner. Serves as a link between cell surface receptors and Rap/Ras GTPases in intracellular signaling cascades. Acts also as an effector for Rap1 by direct association with Rap1-GTP thereby leading to the amplification of Rap1-mediated signaling. Shows weak activity on HRAS. It is controversial whether RAPGEF2 binds cAMP and cGMP or not. Its binding to ligand-activated beta-1 adrenergic receptor ADRB1 leads to the Ras activation through the G(s)-alpha signaling pathway. Involved in the cAMP-induced Ras and Erk1/2 signaling pathway that leads to sustained inhibition of long term melanogenesis by reducing dendrite extension and melanin synthesis. Provides also inhibitory signals for cell proliferation of melanoma cells and promotes their apoptosis in a cAMP-independent nanner. Regulates cAMP-induced neuritogenesis by mediating the Rap1/B-Raf/ERK signaling through a pathway that is independent on both PKA and RAPGEF3/RAPGEF4. Involved in neuron migration and in the formation of the major forebrain fiber connections forming the corpus callosum, the anterior commissure and the hippocampal commissure during brain development. Involved in neuronal growth factor (NGF)-induced sustained activation of Rap1 at late endosomes and in brain-derived neurotrophic factor (BDNF)-induced axon outgrowth of hippocampal neurons. Plays a role in the regulation of embryonic blood vessel formation and in the establishment of basal junction integrity and endothelial barrier function. May be involved in the regulation of the vascular endothelial growth factor receptor KDR and cadherin CDH5 expression at allantois endothelial cell-cell junctions.
Gene References into Functions
Cdk5-mediated phosphorylation of RapGEF2 controls neuronal migration in the developing cerebral cortex.PMID:25189171
local accumulation of PDZGEF at the apical membrane during establishment of epithelial polarity is mediated by electrostatic interactions between positively charged side chains in the PDZ domain and negatively charged phosphatidic acid.PMID:24858808
SCF(FBXW11) bound, polyubiquitylated, and destabilized RAPGEF2, a guanine nucleotide exchange factor that activates the small GTPase RAP1PMID:25332235
NEDD4-1 regulates cell migration and invasion through ubiquitination of CNrasGEF in vitro.PMID:24340059
We report that in response to factors that promote cell motility, the Rap guanine exchange factor RAPGEF2 is rapidly phosphorylated by I-kappa-B-kinase-beta and casein kinase-1alpha and consequently degraded by the proteasome.PMID:24290981
Data indicate that expression of Rapgef2 in embryonic kidney 293T cells enables cAMP-Rap1-ERK signaling.PMID:23800469
DNA methylation shows genome-wide association of NFIX, RAPGEF2 and MSRB3 with gestational age at birth.PMID:22422452
PDZ-GEF activates Rap1 under resting conditions to stabilize cell-cell junctions and maintain basal integrityPMID:21840392
Regulation of G protein-linked guanine nucleotide exchange factors for Rho, PDZ-RhoGEF, and LARG by tyrosine phosphorylation: evidence of a role for focal adhesion kinasePMID:11799111
PSD-95/Dlg/ZO-1 homology (PDZ)-RhoGEF was isolated from mouse brain as a plexin-B1-specific interacting proteinPMID:12196628
Data show that the interaction of PDZ-GEF1 with an internalized neurotrophin receptor transported to late endosomes induces sustained activation of both Rap1 and ERK and neurite outgrowth.PMID:17724123
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Subcellular Location
Cytoplasm. Cytoplasm, perinuclear region. Cell membrane. Late endosome. Cell junction.
Protein Families
RAPGEF2 family
Tissue Specificity
Expressed in primary neuronal and endocrine cells (at protein level). Highest expression levels in brain. Lower expression levels in heart, kidney, lung, placenta and blood leukocytes.