Phospho-IRS1-S636/639 Rabbit pAb for WB, ELISA - P35568

Core Product Specifications and Parameters

Biological Background: IRS1 Function and Localization

• Insulin receptor substrate 1 (IRS1, also known as HIRS-1) is a key signaling adapter protein that mediates signal transduction from the insulin receptor (INSR) and insulin-like growth factor I receptor (IGF1R), playing crucial roles in development, growth, glucose homeostasis, and lipid metabolism. Related references: PMID:7541045, PMID:33991522, PMID:38625937, PMID:19639489
• Upon phosphorylation by activated receptors, IRS1 serves as a scaffold that recruits SH2 domain-containing proteins such as the p85 regulatory subunit of PI3K, GRB2, NCK1/2, and SHP2, thereby propagating downstream signaling cascades. Related references: PMID:11171109, PMID:8265614
• Recruitment of GRB2 leads to activation of the Ras/Raf/MEK/MAPK pathway, which cooperates with the PI3K/AKT pathway to regulate gene expression, cell growth, and differentiation.
• IRS1 positively regulates the Wnt/beta-catenin signaling pathway by suppressing DVL2 autophagy-mediated degradation, thereby promoting cell proliferation. Related references: PMID:24616100
• The protein localizes to both the cytoplasm and nucleus, consistent with its roles in signal transduction and transcriptional regulation.
• IRS1 is extensively phosphorylated at multiple serine/threonine and tyrosine residues; its dysregulation is associated with insulin resistance and diabetes mellitus (Keyword: Diabetes mellitus, Phosphoprotein).

Experimental Guidance and Technical Tips

• This antibody specifically recognizes IRS1 phosphorylated at Ser636 and Ser639; ensure samples are appropriately stimulated (e.g., with insulin) to induce phosphorylation prior to detection.
• For Western blotting, consider using phospho-specific lysis buffers and adding phosphatase inhibitors to preserve the phosphorylation state.
• Validate antibody specificity by comparing signals in phosphatase-treated versus untreated samples, or by peptide blocking with the non-phosphorylated immunogen.
• The predicted molecular weight of IRS1 is 132 kDa; use an appropriate gel percentage and transfer membrane optimized for high-molecular-weight proteins.
• This antibody has been reported for WB and ELISA; other applications may require further optimization.

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