Mouse Anti-INSR Recombinant Antibody (CBT2393) (V2LY-0625-LY1813)

Insulin Receptor

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. In adipocytes, inhibits lipolysis (By similarity).

Activation of protein kinase activityManual Assertion Based On ExperimentIMP:BHF-UCL
Activation of protein kinase B activityManual Assertion Based On ExperimentIDA:BHF-UCL
Adrenal gland developmentIEA:Ensembl
Amyloid-beta clearanceBy SimilarityISS:ARUK-UCL
Carbohydrate metabolic processIEA:UniProtKB-KW
Cellular response to growth factor stimulusIEA:Ensembl
Cellular response to insulin stimulusManual Assertion Based On ExperimentIDA:BHF-UCL
Dendritic spine maintenanceBy SimilarityISS:ARUK-UCL
Epidermis developmentIEA:Ensembl
Exocrine pancreas developmentIEA:Ensembl
G protein-coupled receptor signaling pathwayManual Assertion Based On ExperimentIDA:BHF-UCL
Glucose homeostasisManual Assertion Based On ExperimentIMP:BHF-UCL
Heart morphogenesisManual Assertion Based On ExperimentIMP:BHF-UCL
Insulin receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
LearningManual Assertion Based On ExperimentTAS:ARUK-UCL
Male gonad developmentIEA:Ensembl
Male sex determinationIEA:Ensembl
MemoryManual Assertion Based On ExperimentTAS:ARUK-UCL
Neuron projection maintenanceISS:ARUK-UCL
Peptidyl-tyrosine autophosphorylationIEA:Ensembl
Peptidyl-tyrosine phosphorylationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of cell migrationManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of cell population proliferationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of developmental growthManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of glucose importManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of glycogen biosynthetic processManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of glycolytic processManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of kinase activityManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of MAP kinase activityManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of MAPK cascadeManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of meiotic cell cycleIEA:Ensembl
Positive regulation of mitotic nuclear divisionManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of nitric oxide biosynthetic processManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of phosphatidylinositol 3-kinase signalingManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of protein kinase B signalingManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of protein phosphorylationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of protein-containing complex disassemblyBy SimilarityISS:ARUK-UCL
Positive regulation of receptor internalizationManual Assertion Based On ExperimentIDA:CACAO
Positive regulation of respiratory burstManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of transcription, DNA-templatedIEA:Ensembl
Protein autophosphorylationManual Assertion Based On ExperimentIDA:BHF-UCL
Protein phosphorylationManual Assertion Based On ExperimentTAS:ARUK-UCL
Receptor-mediated endocytosisBy SimilarityISS:ARUK-UCL
Regulation of embryonic developmentManual Assertion Based On ExperimentIMP:BHF-UCL
Regulation of female gonad developmentIEA:Ensembl
Regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIMP:BHF-UCL
Transmembrane receptor protein tyrosine kinase signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Transport across blood-brain barrier2 PublicationsNAS:ARUK-UCL
Viral entry into host cellManual Assertion Based On ExperimentIMP:BHF-UCL

Cell membrane; Late endosome; Lysosome. Binding of insulin to INSR induces internalization and lysosomal degradation of the receptor, a means for down-regulating this signaling pathway after stimulation. In the presence of SORL1, internalized INSR molecules are redirected back to the cell surface, thereby preventing their lysosomal catabolism and strengthening insulin signal reception.

Rabson-Mendenhall syndrome (RMS):
Severe insulin resistance syndrome characterized by insulin-resistant diabetes mellitus with pineal hyperplasia and somatic abnormalities. Typical features include coarse, senile-appearing facies, dental and skin abnormalities, abdominal distension, and phallic enlargement. Inheritance is autosomal recessive.
Leprechaunism (LEPRCH):
Represents the most severe form of insulin resistance syndrome, characterized by intrauterine and postnatal growth retardation and death in early infancy. Inheritance is autosomal recessive.
Diabetes mellitus, non-insulin-dependent (NIDDM):
A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
Familial hyperinsulinemic hypoglycemia 5 (HHF5):
Familial hyperinsulinemic hypoglycemia [MIM:256450], also referred to as congenital hyperinsulinism, nesidioblastosis, or persistent hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels.
Insulin-resistant diabetes mellitus with acanthosis nigricans type A (IRAN type A):
Characterized by the association of severe insulin resistance (manifested by marked hyperinsulinemia and a failure to respond to exogenous insulin) with the skin lesion acanthosis nigricans and ovarian hyperandrogenism in adolescent female subjects. Women frequently present with hirsutism, acne, amenorrhea or oligomenorrhea, and virilization. This syndrome is different from the type B that has been demonstrated to be secondary to the presence of circulating autoantibodies against the insulin receptor.

Extracellular: 763-956
Helical: 957-979
Cytoplasmic: 980-1382

After being transported from the endoplasmic reticulum to the Golgi apparatus, the single glycosylated precursor is further glycosylated and then cleaved, followed by its transport to the plasma membrane.
Autophosphorylated on tyrosine residues in response to insulin. Phosphorylation of Tyr-999 is required for binding to IRS1, SHC1 and STAT5B. Dephosphorylated by PTPRE at Tyr-999, Tyr-1185, Tyr-1189 and Tyr-1190. Dephosphorylated by PTPRF and PTPN1. Dephosphorylated by PTPN2; down-regulates insulin-induced signaling.