Phospho-Insulin R (T1375) Polyclonal Antibody, 100µg, (ATB-P0422)

Description

Background:

After removal of the precursor signal peptide, the insulin receptor precursor is post-translationally cleaved into two chains (alpha and beta) that are covalently linked. Binding of insulin to the insulin receptor (INSR) stimulates glucose uptake. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosines residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin.

Product datasheet:

Overview
Product Description	Phospho-Insulin R (T1375) Polyclonal Antibody, 100µg, (ATB-P0422)
Image
Species Reactivities	Human,Mouse,Rat
Immunogen	Synthesized peptide derived from human Insulin R around the phosphorylation site of T1375.
Properties
Form	Liquid in PBS containing 50% glycerol, 0.5% BSA and 0.02% sodium azide.
Storage Instructions	-20°C/1 year
Clonality	Polyclonal

References:

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2. Relationship between tyrosine phosphorylation and protein expression of insulin receptor and insulin resistance in gestational diabetes mellitus. Chu YL, et al. J Huazhong Univ Sci Technolog Med Sci, 2014 Jun. PMID 24939305
3. Insulin receptor activation with transmembrane domain ligands. Lee J, et al. J Biol Chem, 2014 Jul 11. PMID 24867955
4. Polycystic ovary syndrome: association of a C/T single nucleotide polymorphism at tyrosine kinase domain of insulin receptor gene with pathogenesis among lean Japanese women. Kashima K, et al. J Reprod Med, 2013 Nov-Dec. PMID 24568043
5. Development of in vitro model of insulin receptor cleavage induced by high glucose in HepG2 cells. Yuasa T, et al. Biochem Biophys Res Commun, 2014 Feb 28. PMID 24508798
6. The human insulin receptor cDNA: the structural basis for hormone-activated transmembrane signalling.
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   Nature 313:756-761(1985) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), PROTEIN SEQUENCE OF 28-49 AND 763-782, GLYCOSYLATION AT ASN-43 AND ASN-769, VARIANT GLY-2.
8. Chen E.Y.
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    Nature 428:529-535(2004) [PubMed] [Europe PMC]

    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].