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INSR / Insulin Receptor

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 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.

Gene Name: insulin receptor
Family/Subfamily: Protein Kinase , Insulin receptor
Synonyms: INSR, CD220, ILP receptor, Insulin receptor, IR, HHF5, CD220 antigen
Target Sequences: NM_000208 NP_000199.2 P06213

Publications (2)

1
Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer. Ireland L, Santos A, Campbell F, Figueiredo C, Hammond D, Ellies LG, Weyer-Czernilofsky U, Bogenrieder T, Schmid M, Mielgo A. Oncogene. 2018 April;37:2022-2036. (Human) [Full Text Article] [PubMed:29367764] [PMC:PMC5895608]
2
Unique expression pattern of the three insulin receptor family members in the rat mammary gland: dominance of IGF-1R and IRR over the IR, and cyclical IGF-1R expression. Henning Hvid, Robert Klopfleisch, Sara Vienberg, Bo F Hansen, Inger Thorup, Henrik E Jensen, Martin B Oleksiewicz. Journal of applied toxicology : JAT. 2011 May;31:312-28. [Full Text Article] [PubMed:21259294]

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Proteins (19)
Over-Expression Cell Culture Supernatant (1)
Over-Expression Lysate (6)
Recombinant (12)
INSR / Insulin Receptor (19)
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ELISA (1)
Func (1)
SDS-PAGE (1)
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6His, N-terminus (3)
6His-SUMO, N-terminus (1)
DDK (Flag)-His, C-terminus (1)
GST, N-terminus (1)
His (6)
His,C-terminus (1)
His-GST (1)
His-T7 (1)
Myc-DDK (Flag) (4)
Human (15)
Mouse (1)
Rat (1)
293T Cells (2)
Baculovirus (1)
E. coli (6)
HEK 293 Cells (7)
Human Cells (2)
Wheat Germ Extract (1)
Purified (2)
Low endotoxin level (4)
Biologically active (1)
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HEK 293 Cells
6His, N-terminus
112 kDa
100 µg/$298
INSR / Insulin Receptor Protein
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HEK 293 Cells
His,C-terminus
Bind ELISA Func SDS-PAGE
Biologically active
Less than 1.0 EU/µg protein (determined by LAL method).
The secreted recombinant human INSR isoform short consists of 928 amino acids and has a predicted molecular mass of 106 (83+23) kDa. As a result of glycosylation, the apparent molecular mass of rhINSR is approximately 125-135 kDa & 40-45 kDa, corresponding to the a subunit and the ECD of ß subunit respectively in SDS-PAGE under reducing conditions.
100 µg/$441; 1 mg/$2,003
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HEK 293 Cells
6His, N-terminus
46 kDa
100 µg/$298
INSR / Insulin Receptor Protein - 12.5% SDS-PAGE Stained with Coomassie Blue.
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Wheat Germ Extract
GST, N-terminus
10 µg/$479; 25 µg/$670
INSR / Insulin Receptor Protein - Recombinant Insulin Receptor By SDS-PAGE
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E. coli
His
39.6 kDa
10 µg/$267; 50 µg/$352; 100 µg/$562; 200 µg/$702; 1 mg/$1,723; 500 µg/$1,298; 5 mg/$2,673; 2 mg/$1,900
INSR / Insulin Receptor Protein - Recombinant Insulin Receptor By SDS-PAGE
Select
E. coli
His
32.6 kDa
10 µg/$282; 50 µg/$450; 100 µg/$717; 200 µg/$897; 1 mg/$2,010; 500 µg/$1,547; 5 mg/$3,137; 2 mg/$2,198
INSR / Insulin Receptor Protein - Western validation with an anti-DDK antibody * L: Control HEK293 lysate R: Over-expression lysate
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HEK 293 Cells
Myc-DDK (Flag)
156.33 kDa
100 µg/$710
INSR / Insulin Receptor Protein - Western validation with an anti-DDK antibody * L: Control HEK293 lysate R: Over-expression lysate
Select
HEK 293 Cells
Myc-DDK (Flag)
156.33 kDa
100 µg/$710
INSR / Insulin Receptor Protein
Select
HEK 293 Cells
DDK (Flag)-His, C-terminus
25 kDa
20 µg/$1,107
Select
HEK 293 Cells
6His, N-terminus
112 kDa
200 µl/$283
INSR / Insulin Receptor Protein - (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
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E. coli
6His-SUMO, N-terminus
1 mg/$1,355; 100 µg/$420; 20 µg/$323
Select
293T Cells
Myc-DDK (Flag)
156.33 kDa
20 µg/$215
INSR / Insulin Receptor Protein - Western validation with an anti-DDK antibody * L: Control HEK293 lysate R: Over-expression lysate
Select
293T Cells
Myc-DDK (Flag)
156.33 kDa
20 µg/$215
Select
Baculovirus
His-GST
Less than 1.0 EU/µg protein (determined by LAL method).
72.3 kDa
50 µg/$707
Select
Human Cells
His
Less than 1.0 EU/µg protein (determined by LAL method).
106 kDa
100 µg/$721
Select
Human Cells
His
Less than 1.0 EU/µg protein (determined by LAL method).
107 kDa
100 µg/$721; 1 mg/$4,701
INSR / Insulin Receptor Protein - Recombinant Insulin Receptor By SDS-PAGE
Select
E. coli
His-T7
34.6 kDa
10 µg/$267; 50 µg/$352; 100 µg/$562; 200 µg/$702; 1 mg/$1,723; 500 µg/$1,298; 5 mg/$2,673; 2 mg/$1,900
INSR / Insulin Receptor Protein - Recombinant Insulin Receptor By SDS-PAGE
Select
E. coli
His
38.0 kDa
10 µg/$267; 50 µg/$352; 100 µg/$562; 200 µg/$702; 1 mg/$1,723; 500 µg/$1,298; 5 mg/$2,673; 2 mg/$1,900
INSR / Insulin Receptor Protein - Recombinant Insulin Receptor By SDS-PAGE
Select
E. coli
His
32.3 kDa
10 µg/$279; 50 µg/$432; 100 µg/$690; 200 µg/$862; 1 mg/$1,962; 500 µg/$1,505; 5 mg/$3,011; 2 mg/$2,148
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The data on this page has been compiled from LifeSpan internal sources, the National Center for Biotechnology Information (NCBI), and The Universal Protein Resource (UniProt).