GRB14 Antibody
Description
Definition and Basic Properties
GRB14 antibody refers to monoclonal or polyclonal antibodies that specifically bind to GRB14, a 60 kDa adapter protein encoded by the GRB14 gene . These antibodies are critical for identifying GRB14 in experimental settings, enabling researchers to investigate its expression, interactions, and functional roles.
Key Uses in Studies
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Insulin Signaling Modulation: GRB14 antibodies validate GRB14’s inhibitory role in IR activation. For example, co-immunoprecipitation experiments using GRB14 antibodies confirmed that compound C8 disrupts GRB14-IR binding, enhancing insulin signaling .
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Metabolic Disease Models: Elevated GRB14 levels in adipose tissue of diabetic patients correlate with insulin resistance, making these antibodies vital for studying metabolic dysregulation .
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Retinal Function: GRB14 antibodies identified light-dependent phosphorylation of GRB14 in retinal tissues, linking it to photoreceptor signaling and PTP1B inhibition .
Mechanistic Insights into GRB14-IR Interaction
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GRB14 antibodies revealed that the BPS domain binds IR’s kinase domain, blocking substrate access and reducing catalytic activity .
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Mutagenesis studies using GRB14 antibodies showed that residues like Trp406 and Leu404 are critical for binding specificity .
Therapeutic Potential
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In ob/ob mice (a type II diabetes model), GRB14 antibodies detected increased GRB14 expression in adipose tissue, supporting its role in insulin resistance .
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Inhibiting GRB14-IR interaction with small molecules (e.g., C8) enhanced insulin signaling, as validated by GRB14 antibody-based assays .
Challenges and Limitations
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Tissue Specificity: GRB14 expression varies across tissues, necessitating rigorous validation in model systems .
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Phosphorylation-Dependent Interactions: GRB14’s binding to PTP1B or IR is modulated by tyrosine phosphorylation, complicating assay design .
Future Directions
GRB14 antibodies will remain pivotal in exploring:
Product Specs
Target Background
- Genetic risk for type 2 diabetes (T2D) may influence susceptibility to air pollution through alterations in insulin sensitivity. This has been observed in a study investigating the modification of the association between air pollution and diabetes by a genetic risk score encompassing 63 T2D genes. Five single variants near GRB14, UBE2E2, PTPRD, VPS26A, and KCNQ1 showed nominally significant interactions with PM10 (P<0.05). PMID: 27281273
- The N-terminus of the BPS domain plays a critical role in regulating the formation of the human Grb14 and insulin receptor complex through phosphorylation, alongside other domains. PMID: 28130417
- Elevated GRB14 levels in colorectal cancer patients have been associated with shorter survival. GRB14 upregulation is observed at an advanced clinical stage, correlating with enhanced tumor invasion and lymph node metastasis. PMID: 26965150
- Phosphorylation of the Grb14 BPS domain by GSK-3 is associated with complex formation between Grb14 and the insulin receptor. PMID: 24535599
- Genes within recently identified loci associated with waist-hip ratio (WHR) exhibit fat depot-specific mRNA expression, which correlates with obesity-related traits. Adipose tissue (AT) mRNA expression of 6 genes (TBX15/WARS2, STAB1, PIGC, ZNRF3, GRB14 PMID: 23670221
- Grb14 protein has been shown to modulate mouse rod photoreceptor responses. PMID: 24273167
- Genetic variants ANKRD55 rs459193 and GRB14 rs13389219 have been associated with insulin resistance. PMID: 23457408
- Grb14 serves as the first negative regulator of CEACAM3-initiated bacterial phagocytosis, potentially contributing to the focus of granulocyte responses to specific pathogen-host cell contact sites. PMID: 22948154
- A novel role for Grb14 in fine-tuning receptor signaling and modulating thyroid cancer progression has been proposed. PMID: 22158039
- GRB14 acts as an adapter protein, recruiting 3-phosphoinositede-dependent kinase-1 to the activated insulin receptor, thereby promoting Akt phosphorylation and the transduction of the insulin signal. PMID: 15210700
- The regulation of GRB14 expression levels in response to hormonal stimuli aligns with its role as a repressor of insulin signaling, where it is induced as a negative feedback mechanism. PMID: 15372466
- GRB14 may regulate signaling through the insulin receptor by controlling its tyrosine dephosphorylation in a site-specific manner. PMID: 16582879
- GRB14 is a weight-loss-responsive gene in skeletal muscle. Its transcriptional modulation upon weight loss may improve insulin signaling. PMID: 16849634
- GRB14 regulates insulin action at two levels: through insulin receptor binding and by interfering with downstream pathways. PMID: 19359342
