antibody

Phospho-INSR (Y1185) Antibody

MBS9204291

0.08 mL

165 USD

polyclonal

rabbit

nonconjugated

human, mouse, rat

ELISA, enzyme immunoassay, dot blot

Antibody

Phospho-INSR (Y1185) Antibody

[Phospho-INSR (Y1185)]

[Insulin receptor; IR; CD220; Insulin receptor subunit alpha; Insulin receptor subunit beta; INSR]

[insulin receptor isoform Long preproprotein; Insulin receptor; insulin receptor; insulin receptor; CD_antigen: CD220]

[INSR]

[INSR; INSR; HHF5; CD220; IR]

INSR_HUMAN

Polyclonal

Rabbit Ig

Rabbit

Human (Predicted Reactivity: Bovine, Mouse, Rat, Xenopus, Drosophila)

1,370

This INSR Antibody is generated from rabbits immunized with a KLH conjugated synthetic phosphopeptide corresponding to amino acid residues surrounding Y1185 of human INSR.

Peptide Affinity Purified Rabbit Polyclonal Antibody (Pab)

Purified polyclonal antibody supplied in PBS with 0.09% (W/V) sodium azide. This antibody is purified through a protein A column, followed by peptide affinity purification.

Maintain refrigerated at 2-8 degree C for up to 2 weeks. For long term storage store at -20 degree C in small aliquots to prevent freeze-thaw cycles.

Dot Blot (DB), ELISA (EIA)

DB~~1:500

Dot Blot (DB)

Function: 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: antiapoptotic 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.

Cellular Location: Cell membrane; Single-pass type I membrane protein. Tissue Location: 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. IsoformShort is preferentially expressed in fetal cellssuch as fetal fibroblasts, muscle, liver andkidney. Found as a hybrid receptor withIGF1R in muscle, heart, kidney, adiposetissue, skeletal muscle, hepatoma,fibroblasts, spleen and placenta (at proteinlevel). Overexpressed in several tumors,including breast, colon, lung, ovary, and thyroid carcinomas.

Cancer; Cardiovascular; Metabolism; Neuroscience; Signal Transduction; Phospho Antibodies

Binding of insulin to the insulin receptor (INSR) stimulates glucose uptake, thereby mediating the metabolic functions of insulin. Binding to insulin stimulates association of the receptor with downstream mediators including IRS1 and phosphatidylinositol 3'-kinase (PI3K). This protein can activate PI3K either directly by binding to the p85 regulatory subunit, or indirectly via IRS1. 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.

Nakamaru, K., et al., Biochem. Biophys. Res. Commun. 328(2):449-454 (2005). Diaz, E., et al., Clin. Biochem. 38(3):243-247 (2005). McGettrick, A.J., et al., J. Biol. Chem. 280(8):6441-6446 (2005). Schmitt, T.L., et al., J. Biol. Chem. 280(5):3795-3801 (2005). Denley, A., et al., Mol. Endocrinol. 18(10):2502-2512 (2004).

119395736

P06213

NM_000208.2

Q9PVZ4

156333

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]

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 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 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: Protein kinase, TK; Protein kinase, tyrosine (receptor); Kinase, protein; EC 2.7.10.1; Membrane protein, integral; TK group; InsR family. Chromosomal Location of Human Ortholog: 19p13.3-p13.2. Cellular Component: membrane; intracellular membrane-bound organelle; integral to plasma membrane; plasma membrane; endosome membrane; caveola; receptor complex. Molecular Function: insulin binding; insulin-like growth factor receptor binding; protein binding; insulin-like growth factor I binding; GTP binding; insulin receptor substrate binding; protein-tyrosine kinase activity; PTB domain binding; phosphoinositide 3-kinase binding; receptor signaling protein tyrosine kinase activity; insulin-like growth factor II binding; ATP binding; insulin receptor activity. Biological Process: heart morphogenesis; epidermis development; positive regulation of nitric oxide biosynthetic process; peptidyl-tyrosine phosphorylation; activation of MAPK activity; protein amino acid autophosphorylation; regulation of embryonic development; positive regulation of glycogen biosynthetic process; exocrine pancreas development; glucose homeostasis; positive regulation of glucose import; positive regulation of MAPKKK cascade; regulation of transcription, DNA-dependent; male sex determination; positive regulation of cell proliferation; protein heterotetramerization; positive regulation of developmental growth; positive regulation of mitosis; activation of protein kinase B; G-protein coupled receptor protein signaling pathway; positive regulation of protein kinase B signaling cascade; cellular response to insulin stimulus; positive regulation of glycolysis; carbohydrate metabolic process; insulin receptor signaling pathway; activation of protein kinase activity; positive regulation of protein amino acid phosphorylation; positive regulation of DNA replication; transformation of host cell by virus; positive regulation of cell migration. Disease: Diabetes Mellitus, Insulin-resistant, With Acanthosis Nigricans; Hyperinsulinemic Hypoglycemia, Familial, 5; Pineal Hyperplasia, Insulin-resistant Diabetes Mellitus, And Somatic Abnormalities; Donohue Syndrome

0.08 mL

165 USD

0.4 mL

370