RAPGEF1 Antibody

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Description

Definition and Biological Context

RAPGEF1 (Rap Guanine Nucleotide Exchange Factor 1), also known as C3G or GRF2, is a guanine nucleotide exchange factor (GEF) that activates small GTPases like Rap1. These GTPases regulate processes such as cell adhesion, migration, and differentiation . The RAPGEF1 antibody is designed to bind specifically to this protein, facilitating its detection and functional analysis in experimental settings .

Role in Cellular Signaling

  • ERK1/2 Pathway Activation: RAPGEF1 mediates inorganic phosphate (Pi)-induced ERK1/2 phosphorylation via a Rap1/B-Raf/Mek1/2 cascade in vascular smooth muscle cells, influencing phenotype changes .

  • miR-203 Interaction: RAPGEF1 is a direct target of miR-203, which suppresses keratinocyte proliferation and promotes differentiation .

Disease Implications

  • Cancer:
    RAPGEF1 exhibits dual roles in tumorigenesis, acting as either an oncogene or tumor suppressor depending on context :

Cancer TypeRoleMechanismReference
Pancreatic CancerPro-metastaticActivates Rap1-GTP and EGFR signaling to drive migration
MelanomaPro-invasivePromotes MMP9 production and ERK activation
Bladder CancerTumor suppressorSuppresses migration via Rap1-GTP inhibition
Breast CancerProliferation driverEnhances β1-integrin signaling and invasiveness
  • Neurological and Developmental Roles:
    Zebrafish studies show that RAPGEF1 is essential for early embryonic morphogenesis, including brain and somite development .

Applications in Research

  • Western Blot: Validated for detecting RAPGEF1 in human, mouse, and rat tissues (e.g., mouse liver) .

  • Immunohistochemistry: Used to localize RAPGEF1 in paraffin-embedded human pancreas tissue .

  • Functional Studies: Silencing RAPGEF1 with siRNA reduces ERK1/2 phosphorylation and alters gene expression in vascular cells .

Post-Translational Modifications

RAPGEF1 undergoes extensive phosphorylation and ubiquitination, modulating its activity:

Modification SiteTypeEnzyme/PathwayFunctional Impact
Y504PhosphorylationABL1, SRC, HCKEnhances RapGEF activity
S820PhosphorylationUncharacterizedPotential regulatory role
K683, K808, K869UbiquitinationUnknownMay influence protein stability

Technical Considerations

  • Validation: Antibodies are verified using recombinant protein expression and tissue-specific staining .

  • Cross-Reactivity: No significant cross-reactivity reported with non-target proteins in human, mouse, or rat samples .

  • Limitations: Some isoforms may not be detected due to splice variants .

Product Specs

Buffer
Preservative: 0.03% Proclin 300
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Form
Liquid
Lead Time
Typically, we can ship your orders within 1-3 business days of receiving them. Delivery times may vary based on the shipping method and destination. Please consult your local distributor for specific delivery times.
Synonyms
C3G antibody; C3G protein antibody; CRK SH3 binding GNRP antibody; CRK SH3-binding GNRP antibody; DKFZp781P1719 antibody; GRF 2 antibody; GRF2 antibody; Guanine nucleotide releasing factor 2 (specific for crk proto oncogene) antibody; Guanine nucleotide releasing factor 2 antibody; Guanine nucleotide-releasing factor 2 antibody; OTTHUMP00000064558 antibody; Protein C3G antibody; Rap guanine nucleotide exchange factor (GEF) 1 antibody; Rap guanine nucleotide exchange factor 1 antibody; RAPGEF 1 antibody; RAPGEF1 antibody; RPGF1_HUMAN antibody
Target Names
Uniprot No.

Target Background

Function
RAPGEF1 (C3G) is a guanine nucleotide-releasing protein that interacts with the SH3 domains of CRK and GRB2/ASH. It plays a crucial role in signal transduction from CRK, activating RAS. RAPGEF1 is involved in cell branching and adhesion processes mediated by the BCAR1-CRK-RAPGEF1 signaling pathway, as well as the activation of RAP1. Additionally, it contributes to the establishment of basal endothelial barrier function. RAPGEF1 is implicated in nerve growth factor (NGF)-induced sustained activation of Rap1 and neurite outgrowth.
Gene References Into Functions
  1. Our research reveals novel mechanisms by which C3G regulates critical aspects of tumorigenesis. PMID: 27286263
  2. C3G/RAP1 activity is involved in the metastatic spread of epithelial ovarian cancer. PMID: 25617801
  3. C3G plays a significant role in platelet clotting through a mechanism involving its GEF activity, suggesting potential involvement in neutrophil development. PMID: 22659131
  4. A study using the human neuroblastoma cell line investigated the possibility of cellular phospho-C3G (pC3G) as a substrate of the intracellular T-cell protein tyrosine phosphatase TC-PTP (PTPN2). PMID: 21876762
  5. Lyn regulates the spatial activation of Rap1 by recruiting the CrkL-C3G protein complex to the leading edge. PMID: 21628423
  6. Somatic demethylation of a relaxed-criterion CpG island (CGI-B) located in the first intron of RAPGEF1 was observed in 40% of colon cancers and 8% of gastric cancers compared to their matching normal tissues, which were always methylated. PMID: 21399874
  7. Data indicated that the polymorphism in TP53 (rs1042522) was associated with type 2 diabetes, and that potential interactions of TP53 (rs1042522) with RAPGEF1 (rs11243444) or NRF1 (rs1882095) increased the risk of type 2 diabetes. PMID: 21146886
  8. A significant positive correlation was found between layers II and IV of the dorso-lateral prefrontal cortex in the percentage of MR-GEF expressing neurons in individuals with bipolar disorder. PMID: 20436929
  9. C3G overexpression induces neurite-like extensions in MDA-MB-231 and BT549 breast carcinoma cells but not in a variety of other cancer cell lines examined. PMID: 21223981
  10. C3G has been identified as a novel target of c-Abl. PMID: 20581864
  11. ALK activation of Rap1 via the Rap1-specific GEF C3G may contribute to cell proliferation and oncogenesis of neuroblastoma. PMID: 20190816
  12. Cbl-b plays a negative role in Crk-L-C3G-mediated Rap1 and LFA-1 activation in T cells. PMID: 12697763
  13. C3G and Hck interact physically and functionally in vivo to activate kinase-dependent and caspase-mediated apoptosis, which is independent of the catalytic domain of C3G. PMID: 14551197
  14. C3G interferes with at least two distinct aspects of oncogenic transformation - cell cycle progression and loss of contact inhibition. PMID: 15077165
  15. Amplification and increased expression of the C3G gene may play a role in human lung carcinogenesis through disruption of the CRK-Rap1 signaling pathway. PMID: 15138850
  16. Src family kinases or pervanadate treatment induces phosphorylation of C3G on Y504. Unlike C3G, which is primarily cytosolic, pY504C3G localizes to the Golgi and subcortical actin cytoskeleton, suggesting a function for C3G at these cellular compartments. PMID: 15320955
  17. Inactivation of the Crk SH3 domain-binding guanine nucleotide-releasing factor is associated with cervical squamous cell carcinoma. PMID: 16681758
  18. C3G triggers PP2A activation and binding to MEK and ERK at the subcortical actin cytoskeleton, facilitating ERK dephosphorylation. PMID: 17825818
  19. Research identifies a mechanism by which the WAVE2 complex regulates T cell receptor signaling to Rap1 and integrin activation through Abl- and CrkL-C3G. PMID: 18809728
  20. Rap1 and its exchange factor C3G are involved in mediating Fc gammaR-dependent phagocytosis. PMID: 18832707
  21. Genetic polymorphisms in the RAPGEF1 gene and a positive association between one polymorphism and type 2 diabetes in the Korean population were observed. PMID: 19297053
  22. These findings strongly suggest a dual regulatory role for C3G in chronic myeloid leukemia cells, modulating both apoptosis and survival through Rap-dependent and independent mechanisms. PMID: 19324082

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Database Links

HGNC: 4568

OMIM: 600303

KEGG: hsa:2889

STRING: 9606.ENSP00000361264

UniGene: Hs.127897

Subcellular Location
Early endosome.
Tissue Specificity
Ubiquitously expressed in adult and fetus. Expression is high in adult skeletal muscle and placenta and in fetal brain and heart. Low levels of expression in adult and fetal liver.

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