p-IRS-1 Antibody (Ser 374)-R: sc-17193-R

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Insulin receptor substrate-1 (IRS-1) is a substrate of the insulin receptor that undergoes phosphorylation in response to insulin, IGF-1 and IL-4. Tyrosine (Tyr) phosphorylation of IRS-1 mediates insulin-stimulated responses, while Serine (Ser)/Threonine (Thr) phosphorylation of IRS-1 can either enhance or negate insulin effects. Tyrosines 465, 612, 632, 662, 941 and 989 of IRS-1 resemble YXXM motifs that upon phosphorylation are predicted to bind SH2 domains in the p85 regulatory subunit of PI3K, resulting in activation of p110 catalytic subunit. SHP-2 binding to IRS-1 can occur upon phosphorylation at Tyr 1179 and Tyr 1229. GRB2 binding can occur upon phsophoryl-ation at Tyr 896. Rodent Ser 99 and Thr 502 of IRS-1 are casein kinase II-dependent phosphorylation sites. There is an increase in Ser 636 phosphoryl-ation of IRS-1 in primary skeletal muscle cells from patients with type 2 diabetes. IGF-I and anisomycin treatment converge downstream onto FRAP and PKCd to induce IRS-1 Ser 312 phosphorylation. Insulin resistance in the aorta of hypertensive rats is associated with elevated IRS-1 phosphorylation at Ser 307 and increased SAPK/JNK activation. IRS-1 contains three putative binding sites for 14-3-3 protein at Ser 270, Ser 374 and Ser 641 that are capable of phosphorylation.