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Insulin receptor

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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 phosphotyrosine 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.

Below are the list of possible Insulin receptor products. If you cannot find the target and/or product is not available in our catalog, please click here to contact us and request the product or submit your request for custom elisa kit production, custom recombinant protein production or custom antibody production. Custom ELISA Kits, Recombinant Proteins and Antibodies can be designed, manufactured and produced according to the researcher's specifications.
 

Insulin receptor

 Insulin receptor ELISA Kit
 Insulin receptor Recombinant
 Insulin receptor Antibody
Also known as Insulin receptor (IR) (CD antigen CD220).
INSR: a receptor tyrosine kinase that 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 oth
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er 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 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. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). The holoenzyme is cleaved into two chains, the alpha and beta subunits. The active complex is a tetramer containing 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains constitute the ligand- binding domain, while the beta chains carry the kinase domain. Interacts with SORBS1 but dissociates from it following insulin stimulation. Familial mutations associated with insulin resistant diabetes, acanthosis nigricans, pineal hyperplasia, and polycystic ovary syndrome. SNP variants may be associated with polycystic ovary syndrome, atypical migraine and diabetic hyperlipidemia. Mutations also cause leprechaunism, a severe insulin resistance syndrome causing growth retardation and death in early infancy. Two isoforms of the human protein are produced by alternative splicing. The Short isoform has a higher affinity for insulin than the longer. Isoform Long and isoform Short are predominantly expressed in tissue targets of insulin metabolic effects: liver, adipose tissue and skeletal muscle but are also expressed in the peripheral nerve, kidney, pulmonary alveoli, pancreatic acini, placenta vascular endothelium, fibroblasts, monocytes, granulocytes, erythrocytes and skin. Isoform Short is preferentially expressed in fetal cells such as fetal fibroblasts, muscle, liver and kidney. Found as a hybrid receptor with IGF1R in muscle, heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibroblasts, spleen and placenta. Overexpressed in several tumors, including breast, colon, lung, ovary, and thyroid carcinomas.

Protein type: EC 2.7.10.1; InsR family; Kinase, protein; Membrane protein, integral; Protein kinase, TK; Protein kinase, tyrosine (receptor); TK group

Chromosomal Location of Human Ortholog: 19p13.3-p13.2

Cellular Component: caveola; endosome membrane; integral to plasma membrane; intracellular membrane-bound organelle; membrane; plasma membrane; receptor complex

Molecular Function: ATP binding; GTP binding; insulin binding; insulin receptor activity; insulin receptor substrate binding; insulin-like growth factor I binding; insulin-like growth factor II binding; insulin-like growth factor receptor binding; phosphoinositide 3-kinase binding; protein binding; protein-tyrosine kinase activity; PTB domain binding; receptor signaling protein tyrosine kinase activity

Biological Process: activation of MAPK activity; activation of protein kinase activity; activation of protein kinase B; cellular response to insulin stimulus; G-protein coupled receptor protein signaling pathway; glucose homeostasis; heart morphogenesis; insulin receptor signaling pathway; peptidyl-tyrosine phosphorylation; positive regulation of cell migration; positive regulation of cell proliferation; positive regulation of developmental growth; positive regulation of DNA replication; positive regulation of glucose import; positive regulation of glycogen biosynthetic process; positive regulation of glycolysis; positive regulation of MAPKKK cascade; positive regulation of mitosis; positive regulation of nitric oxide biosynthetic process; positive regulation of protein amino acid phosphorylation; positive regulation of protein kinase B signaling cascade; protein amino acid autophosphorylation; protein heterotetramerization; regulation of embryonic development; regulation of transcription, DNA-dependent; transformation of host cell by virus

Disease: Diabetes Mellitus, Insulin-resistant, With Acanthosis Nigricans; Donohue Syndrome; Hyperinsulinemic Hypoglycemia, Familial, 5; Pineal Hyperplasia, Insulin-resistant Diabetes Mellitus, And Somatic Abnormalities
 INSR ELISA Kit
 INSR Recombinant
 INSR Antibody
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