Phospho-GAB2 (Tyr643) Antibody
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Description
Biological Significance of GAB2 Tyr643 Phosphorylation
GAB2 is a scaffolding protein that integrates signals from cytokine/growth factor receptors and antigen receptors. Phosphorylation at Tyr643 enables GAB2 to recruit SHP2 via its C-terminal SH2 domain, facilitating activation of MAPK/ERK and RhoA-dependent pathways . Key roles include:
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IL-2 Signaling: In T lymphocytes, GAB2–SHP2 interaction at Tyr643 is essential for ERK activation and transcriptional regulation of c-fos via the serum response element (SRE) .
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Radiation Response: Low-dose γ-radiation (0.05 Gy) induces phosphorylation of Tyr643 in fibroblasts (MRC-5 and NHDF cells), suggesting its role in stress signaling .
Applications of Phospho-GAB2 (Tyr643) Antibody
This antibody is widely used in molecular research for:
IL-2-Dependent Signaling
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Mutation of Tyr643 to phenylalanine (Y643F) disrupts SHP2 binding, impairing ERK activation and c-fos promoter activity in T cells .
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Dominant-negative Gab2 Y614F/Y643F mutants block SHP2 recruitment and downstream MAPK signaling .
Radiation-Induced Phosphorylation
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Dose-dependent responses of phospho-Gab2 (Tyr643) in fibroblasts:
Cell Line Radiation Dose (Gy) Relative Intensity (vs. Control) MRC-5 0.05 2.2 NHDF 0.05 2.2
Validation and Quality Control
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
Typically, we can ship your orders within 1-3 business days of receipt. Delivery times may vary depending on the purchase method or location. Please consult your local distributors for specific delivery times.
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 is an adapter protein that functions 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. GAB2 is also involved in the regulation of cell proliferation and hematopoiesis.
Gene References Into Functions
- The Alzheimer's disease risk variant rs2373115 is associated with increased NARS2 expression in the brain. GAB2 expression is also elevated in Alzheimer's disease brain tissue. PMID: 30088171
- Knockdown of Gab2 suppressed the activity of both PI3K/AKT and MAPK/ERK pathways in HER2-overexpressing breast cancer cells. PMID: 30326469
- These findings indicate that miR-485 may have tumor suppressive roles in colorectal cancer (CRC) by directly targeting GAB2 and indirectly regulating AKT and ERK signaling pathways. This suggests that miR-485 could be a potential therapeutic target for CRC patients. PMID: 29781037
- Gab2 is overexpressed in uveal melanomas (UMs) and plays a significant role in UM invasion. The findings suggest a novel role for Gab2 in modulating MMP-2, MMP-9, and fascin expression, which ultimately regulates the invasion of UM tumor cells. PMID: 28791340
- A common locus (rs3740677) in the 3' UTR of the GAB2 sequence, which is targeted by the miRNA-185, was explored for its potential association with late-onset Alzheimer's disease (LOAD) in a large-scale case-control study of Chinese Han populations. PMID: 27311772
- The study identified that miR-302c-3p downregulation in human renal cell carcinoma (RCC) cells causes Gab2 overexpression, Akt hyperactivation, and cell proliferation. PMID: 28412750
- The study provided evidence suggesting that GAB2, as an adapter protein, was preferentially induced in Th2 differentiation and regulated Th2 immune responses. PMID: 28477539
- 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 squamous cell carcinoma (SCC) in non-smokers. PMID: 28960030
- Results show that up-regulation of Gab2 expression was found to be 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
- 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. As Gab2 binds to VEGFR2 complexes more transiently than Gab1, VEGFR2 complexes can recycle and continue to participate in other signaling pathways. PMID: 23805312
- The study showed 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
- The study investigated BAK1, SPRY4, and GAB2 SNPs in pediatric germ cell tumors (GCT). A variant in SPRY4 was associated with a reduced risk of GCT. A variant in BAK1 was positively associated with GCT, with a strong estimated effect for testis tumors. A SNP in GAB2 was associated with an increased risk of GCT. PMID: 28295819
- Overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating the expression of CXCL1, CXCL2, and CXCL8, which is IKKbeta-dependent. PMID: 26657155
- GAB2 is a key intermediary between YAP/TAZ and the PI3K/AKT pathway. PMID: 28202507
- The findings of this study suggested that GAB2 rs2373115 may contribute to Alzheimer's disease susceptibility only in the European population but not in the East Asian population. PMID: 28320126
- ERK1 and ERK2 interact with Gab2 via a novel docking motif, which is required for subsequent Gab2 phosphorylation in response to ERK1/2 activation. PMID: 28096188
- 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
- Overexpression of GAB2 suppressed the expression of miR197 in glioblastoma cells. PMID: 27035789
- GAB2 might promote hepatocellular carcinoma (HCC) cell proliferation by enhancing ERK signaling. PMID: 27026230
- Data indicate that the most prominent proteins associating with Gab2 are PTPN11, PIK3R1, and ARID3B. PMID: 27025927
- The study shows that Gab2 is significantly upregulated in metastasis-positive colorectal cancer (CRC) tissues, suggesting that it plays a vital role in regulating CRC metastasis and could be a potential target for diagnosis. PMID: 26754532
- Grb2-associated binder 2 silencing impairs growth and migration of non-small cell lung cancer cells via PI3K-Akt signaling. PMID: 26617767
- Gab2 may be involved in the onset and progression of HCC, but its expression is unable to serve as an independent prognosis factor in HCC patients. PMID: 27544933
- miR125a-5p, acting as a novel Gab2 suppressor, is partly down-regulated by DNA hypermethylation in glioma. PMID: 25598421
- GAB2, GSPT1, TFDP2, and ZFPM1 are four new susceptibility loci for testicular germ cell tumor. PMID: 26503584
- Data indicate 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
- Gab2 expression may play an important role in the progression of colorectal carcinoma. PMID: 26045784
- In colorectal cancer, miR-125b mediates PAR2-induced cancer cell migration by targeting Gab2. PMID: 26354435
- Upregulations of Gab1 and Gab2 proteins are associated with tumor progression of human gliomas. PMID: 24998422
- Down-regulation of Gab2 has a protective function during M. tuberculosis infection, revealing a potential negative regulatory role for Gab2 in immunity to TB. PMID: 24805943
- Gab2 protein expression was remarkably reduced in the temporal neocortex of TLE patients. PMID: 24327320
- High Gab2 expression is associated with glioma. PMID: 23231021
- GAB2 has a role as an ovarian cancer oncogene, transforming immortalized ovarian and fallopian tube secretory epithelial cells. PMID: 24385586
- The GAB2 gene may be associated with sporadic Alzheimer's disease risk. PMID: 24161894
- Gab2 may protect neurons against late-onset Alzheimer's disease. PMID: 23724096
- Interactions between the GAB2 and GSK3B polymorphisms and the well-established genetic factor APOE may modify the overall risk of Alzheimer's disease. PMID: 23525328
- GAB2 is a novel regulator of tumor angiogenesis in NRAS-driven melanoma. PMID: 22926523
- Results indicate that RSK directly phosphorylates Gab2 on 3 serine residues. Findings show RSK-mediated Gab2 phosphorylation inhibits Shp2 recruitment, suggesting that RSK mediates a negative-feedback loop that attenuates Gab2-dependent functions, including cell motility. PMID: 23401857
- These data underscore the critical roles of Gab1 and Gab2 in IL-22-mediated HaCaT cell proliferation, migration, and differentiation. PMID: 22851227
- These results define a novel role for Gab2 in mediating mucin gene expression and goblet cell hyperplasia (GCH). These findings have important implications for the pathogenesis and therapy of airway inflammatory diseases. PMID: 22859374
- A significant association was found 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
- Gab2 overexpression, via activation of the PI3K-Zeb1 pathway, promotes characteristics of epithelial-to-mesenchymal transition in ovarian cancer cells. PMID: 21996746
- Our findings implicate an association between genetic variations of GAB2 and Alzheimer's disease in Han Chinese. PMID: 21285854
- Both phosphatidylinositol (PI)-3 kinase and SH2 domain-containing protein tyrosine phosphatase (SHP)2 binding sites of Gab2 are required for mast cell degranulation and the anaphylaxis response. PMID: 21653832
- Gab2 is over-expressed in malignant lung tissues. PMID: 21552417
- Gab2 regulates cytoskeletal organization and cell motility by regulating RhoA activation and binding to Shp2. PMID: 21118992
- The findings implicate GAB2 as a susceptibility gene for late-onset Alzheimer's disease in Han Chinese. PMID: 21108942
- This study supports the association between the possibly protective GAB2 haplotype and the risk of late-onset Alzheimer's disease in APOEepsilon4 carriers. PMID: 20888920
- The GAB2 rs2373115 polymorphism was not a significant factor in developing Alzheimer's disease among Mongolians. PMID: 20188796
- Findings indicate that while Gab2 expression is not prognostic in breast cancer, its role in early disease evolution warrants further analysis. PMID: 20087860
Database Links
Protein Families
GAB family
Subcellular Location
Cytoplasm. Cell membrane.
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