Phospho-GAB2 (Tyr452) Antibody

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Description

Definition and Biological Context

Phospho-GAB2 (Tyr452) Antibody is a highly specific reagent designed to detect endogenous levels of GAB2 (GRB2-associated binding protein 2) only when phosphorylated at tyrosine residue 452. GAB2 is an adaptor protein critical for integrating signals from receptors such as cytokine, antigen, and growth factor receptors into downstream pathways like PI3K/AKT and MAPK . Tyr452 phosphorylation creates a binding motif (p-YXXM) for the p85 regulatory subunit of PI3K, enabling activation of AKT and other signaling cascades .

Role in Hormone Signaling

  • FSH Signaling: In ovarian granulosa cells, FSH promotes dephosphorylation of GAB2(Tyr452) while phosphorylating IRS-1(Tyr989), enabling PI3K/AKT activation. Overexpression of GAB2 amplifies FSH-induced AKT phosphorylation, critical for cell survival and differentiation .

  • Regulation by PKA: GAB2 forms a preassembled complex with PI3K and IRS-1. PKA phosphorylates GAB2 at Ser159, enhancing its role in AKT activation .

Mast Cell Activation

  • FcεRI Signaling: In mast cells, FcεRI engagement triggers Gab2(Tyr452) phosphorylation, facilitating PI3K recruitment and downstream MAPK activation (Erk, Jnk, p38). siRNA knockdown of Gab2 reduces TNF-α release and MAPK activity .

  • Synergistic Degranulation: Costimulation of FcεRI and adenosine receptors amplifies Gab2(Tyr452) phosphorylation, driving PI3K-dependent synergistic degranulation. Mutations in FcεRIβ-ITAM disrupt this process .

Phosphorylation Dynamics and Interactions

Post-translational modifications (PTMs) of GAB2:

Modification SiteEnzyme/RegulatorFunctional Outcome
Tyr452HCK (predicted)Binds p85 subunit of PI3K, activating AKT
Ser159AKTNegative feedback to suppress tyrosine phosphorylation
Tyr614ZAP70Facilitates SHP2 association

Interaction partners:

  • PI3K: Direct binding via p85 subunit at Tyr452 .

  • GRB2: SH3 domain-mediated interaction .

  • PKA: Anchors PKA to GAB2-PI3K-IRS-1 complexes .

Validation and Experimental Data

  • Functional Validation:

    • Overexpression of wild-type GAB2 in GCs increases AKT(Ser473) phosphorylation by 82.7% (P < 0.05) .

    • siRNA-mediated Gab2 knockdown reduces FcεRI-induced TNF-α release by 40–50% .

  • Antibody Specificity:

    • Recognizes endogenous phospho-GAB2(Tyr452) in FSH-treated GCs and antigen-stimulated mast cells .

    • No cross-reactivity with non-phosphorylated GAB2 or other tyrosine-phosphorylated proteins .

Product Specs

Form
Rabbit IgG in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol.
Lead Time
Generally, we can ship the products within 1-3 business days after receiving your orders. Delivery time may vary depending on the purchasing method or location. For specific delivery time, please consult your local distributors.
Synonyms
GAB 2 antibody; Gab2 antibody; GAB2_HUMAN antibody; Grb 2 associated binder 2 antibody; GRB 2 associated binding protein 2 antibody; Grb2 associated binder 2 antibody; GRB2 associated binder 2 pp100 antibody; GRB2 associated binding protein 2 antibody; GRB2-associated binder 2 antibody; GRB2-associated-binding protein 2 antibody; Growth factor receptor bound protein 2 associated protein 2 antibody; Growth factor receptor bound protein 2-associated protein 2 antibody; KIAA0571 antibody; p97 antibody; PH domain containing adaptor molecule p97 antibody; pp100 antibody
Target Names
Uniprot No.

Target Background

Function
GAB2 functions as an adapter protein downstream of various membrane receptors, including those for cytokines, antigens, hormones, cell matrix, and growth factors. It plays a crucial role in regulating multiple signaling pathways. GAB2 regulates osteoclast differentiation by mediating the TNFRSF11A/RANK signaling pathway. In allergic responses, it contributes to mast cell activation and degranulation through PI-3-kinase regulation. Furthermore, GAB2 is involved in the regulation of cell proliferation and hematopoiesis.
Gene References Into Functions
  1. The Alzheimer's Disease risk variant rs2373115 has been associated with increased NARS2 expression in the brain. Notably, GAB2 expression is elevated in AD brain tissue. PMID: 30088171
  2. Knockdown of Gab2 suppressed the activity of both PI3K/AKT and MAPK/ERK pathways in HER2-overexpressing breast cancer cells. PMID: 30326469
  3. Research suggests that miR-485 may act as a tumor suppressor in Colorectal cancer (CRC) by directly targeting GAB2 and indirectly regulating AKT and ERK signaling pathways. This finding suggests that miR-485 might be a potential therapeutic target for CRC patients. PMID: 29781037
  4. Gab2 is overexpressed in UMs and plays a significant role in UM invasion. Further investigation suggests a novel function for Gab2 in modulating MMP-2, MMP-9, and fascin expression, thus regulating the invasion of UM tumor cells. PMID: 28791340
  5. A common locus (rs3740677) in the 3' UTR of the GAB2 sequence, targeted by miRNA-185, was explored for its association with the risk of late-onset AD (LOAD) in a large-scale case-control study involving Chinese Han populations. PMID: 27311772
  6. Studies have shown that miR-302c-3p downregulation in human RCC cells leads to Gab2 overexpression, Akt hyperactivation, and cell proliferation. PMID: 28412750
  7. Research identified GAB2 as an adaptor protein preferentially induced in Th2 differentiation and involved in regulating Th2 immune responses. PMID: 28477539
  8. The proto-oncogene GAB2 (11q14.1) was significantly amplified in non-smoker patients, and GAB2 protein was relatively up-regulated in non-smoker tissues compared to smoker tissues. GAB2 may represent a potential biomarker for lung SCC in non-smokers. PMID: 28960030
  9. Results demonstrate that up-regulation of Gab2 expression is positively correlated with VEGF in colorectal cancer (CRC) tissues. This suggests that Gab2 promotes intestinal tumor growth and angiogenesis through upregulation of VEGF expression mediated by the MEK/ERK/c-Myc pathway. PMID: 28420432
  10. The model showed agreement at several key nodes, involving scaffolding proteins Gab1, Gab2, and their complexes with Shp2. VEGFR2 recruitment of Gab1 is greater in magnitude, slower, and more sustained than that of Gab2. Since Gab2 binds VEGFR2 complexes more transiently than Gab1, VEGFR2 complexes can recycle and continue to participate in other signaling pathways. PMID: 23805312
  11. Researchers demonstrated that GAB2 is cleaved at G238 during Coxsackievirus type B3 infection by viral proteinase 2A, generating two cleaved fragments of GAB2-N1-237 and GAB2-C238-676. PMID: 28361043
  12. A study investigated BAK1, SPRY4, and GAB2 SNPs in pediatric germ cell tumors (GCT). The results showed a variant in SPRY4 was associated with reduced GCT risk, a variant in BAK1 was positively associated with GCT with a strong estimated effect for testis tumors, and a SNP in GAB2 was linked to increased GCT risk. PMID: 28295819
  13. Overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating expression of CXCL1, CXCL2, and CXCL8, a process dependent on IKKbeta. PMID: 26657155
  14. GAB2 serves as a key intermediary between YAP/TAZ and the PI3K/AKT pathway. PMID: 28202507
  15. The findings of this study suggest that GAB2 rs2373115 may contribute to Alzheimer's disease susceptibility specifically in European populations but not in East Asian populations. PMID: 28320126
  16. ERK1 and ERK2 interact with Gab2 through a novel docking motif, which is necessary for subsequent Gab2 phosphorylation in response to ERK1/2 activation. PMID: 28096188
  17. GAB2 is a functional downstream target of miR-302a in glioma. GAB2 plays a role in cell proliferation, migration, and invasion of glioma. PMID: 28000880
  18. Overexpression of GAB2 suppressed the expression of miR197 in glioblastoma cells. PMID: 27035789
  19. GAB2 might promote hepatocellular carcinoma (HCC) cell proliferation by enhancing ERK signaling. PMID: 27026230
  20. Data indicate that the most prominent proteins associating with Gab2 are PTPN11, PIK3R1, and ARID3B. PMID: 27025927
  21. A study shows that Gab2 is significantly upregulated in metastasis-positive colorectal cancer (CRC) tissues, suggesting a crucial role in regulating CRC metastasis and a potential target for diagnosis. PMID: 26754532
  22. Grb2-associated binder 2 silencing impairs growth and migration of non-small cell lung cancer cells through PI3K-Akt signaling. PMID: 26617767
  23. Gab2 may be involved in the onset and progression of HCC, but its expression does not serve as an independent prognostic factor in HCC patients. PMID: 27544933
  24. miR125a-5p, acting as a novel Gab2 suppressor, is partly down-regulated by DNA hypermethylation in glioma. PMID: 25598421
  25. GAB2, GSPT1, TFDP2, and ZFPM1 are four newly identified susceptibility loci for testicular germ cell tumor. PMID: 26503584
  26. Data suggest that high-grade serous ovarian carcinoma (HGSC) cell lines with high GRB2 associated binding protein 2 (GAB2) expression are more responsive to phosphatidylinositol 3-kinases (PI3K) inhibitor PF-04691502. PMID: 25852062
  27. Gab2 expression may play a significant role in the progression of colorectal carcinoma. PMID: 26045784
  28. In colorectal cancer, miR-125b mediates PAR2-induced cancer cell migration by targeting Gab2. PMID: 26354435
  29. Upregulations of Gab1 and Gab2 proteins are associated with tumor progression in human gliomas. PMID: 24998422
  30. Down-regulation of Gab2 exhibits a protective function during M. tuberculosis infection, revealing a potential negative regulatory role for Gab2 in immunity to TB. PMID: 24805943
  31. Gab2 protein expression was remarkably reduced in the temporal neocortex of TLE patients. PMID: 24327320
  32. High Gab2 expression is associated with glioma. PMID: 23231021
  33. GAB2 acts as an ovarian cancer oncogene, transforming immortalized ovarian and fallopian tube secretory epithelial cells. PMID: 24385586
  34. The GAB2 gene may be associated with sporadic Alzheimer's disease risk. PMID: 24161894
  35. Gab2 may protect neurons against late-onset Alzheimer's disease. PMID: 23724096
  36. Interactions between the GAB2 and GSK3B polymorphisms and the established genetic factor APOE may modify the overall risk of Alzheimer disease. PMID: 23525328
  37. GAB2 is a novel regulator of tumor angiogenesis in NRAS-driven melanoma. PMID: 22926523
  38. Results indicate that RSK directly phosphorylates Gab2 on 3 serine residues. These findings suggest that RSK-mediated Gab2 phosphorylation inhibits Shp2 recruitment, indicating a negative-feedback loop that attenuates Gab2-dependent functions including cell motility. PMID: 23401857
  39. These data highlight the critical roles of Gab1 and Gab2 in IL-22-mediated HaCaT cell proliferation, migration, and differentiation. PMID: 22851227
  40. These results define a novel role for Gab2 in mediating mucin gene expression and GCH. These findings have significant implications for the pathogenesis and therapy of airway inflammatory diseases. PMID: 22859374
  41. A significant association was observed between the GAB2 gene and morphological brain differences in 755 young adult twins. (GAB2) has been shown to provide a 1.27-1.51 increased odds of developing late Alzheimer's. PMID: 22856364
  42. Gab2 overexpression, through activation of the PI3K-Zeb1 pathway, promotes characteristics of epithelial-to-mesenchymal transition in ovarian cancer cells. PMID: 21996746
  43. Research findings suggest an association between genetic variations of GAB2 and Alzheimer disease in Han Chinese. PMID: 21285854
  44. Both phosphatidylinositol (PI)-3 kinase and SH2 domain-containing protein tyrosine phosphatase (SHP)2 binding sites of Gab2 are essential for mast cell degranulation and the anaphylaxis response. PMID: 21653832
  45. Gab2 is over-expressed in malignant lung tissues. PMID: 21552417
  46. Gab2 regulates cytoskeletal organization and cell motility by controlling RhoA activation and binding to Shp2. PMID: 21118992
  47. Findings suggest that GAB2 is a susceptibility gene for late-onset Alzheimer disease in Han Chinese. PMID: 21108942
  48. This study supports the association between the potentially protective GAB2 haplotype and the risk of late-onset Alzheimer's disease in APOEepsilon4 carriers. PMID: 20888920
  49. The GAB2 rs2373115 polymorphism was not a significant factor in developing Alzheimer disease among Mongolians. PMID: 20188796
  50. Findings suggest that while Gab2 expression is not prognostic in breast cancer, its role in early disease evolution warrants further analysis. PMID: 20087860

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Database Links

HGNC: 14458

OMIM: 606203

KEGG: hsa:9846

STRING: 9606.ENSP00000354952

UniGene: Hs.429434

Protein Families
GAB family
Subcellular Location
Cytoplasm. Cell membrane.

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