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Rabbit Anti-Phospho-Insulin Receptor (Tyr999)  antibody (bs-16680R)  
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產(chǎn)品編號 bs-16680R
英文名稱 Rabbit Anti-Phospho-Insulin Receptor (Tyr999)  antibody
中文名稱 磷酸化胰島素受體抗體
別    名 Insulin Receptor (phospho Y999); p-Insulin Receptor (phospho Y999); CD 220; CD220; CD220 antigen; HHF 5; HHF5; human insulin receptor; INSR; INSR_HUMAN; Insulin receptor subunit beta; IR 1; IR; IR-1; IR1.  
Specific References  (1)     |     bs-16680R has been referenced in 1 publications.
[IF=2.868] Liu B et al. MicroRNA‐379 mediates pigmentation, migration, and proliferation of melanocytes by targeting the insulin‐like growth factor 1 receptor. Exp Dermatol. 2020 May;29(5):467-476.  WB ;  alpaca.  
產(chǎn)品類型 磷酸化抗體 
研究領(lǐng)域 細胞生物  信號轉(zhuǎn)導(dǎo)  生長因子和激素  激酶和磷酸酶  糖尿病  新陳代謝  細胞膜蛋白  
抗體來源 Rabbit
克隆類型 Polyclonal
交叉反應(yīng) Human,Rat (predicted: Cow,Chicken,Horse)
產(chǎn)品應(yīng)用 WB=1:500-2000,IHC-P=1:100-500,IHC-F=1:100-500,Flow-Cyt=1μg/Test,IF=1:100-500
not yet tested in other applications.
optimal dilutions/concentrations should be determined by the end user.
細胞定位 細胞膜 
性    狀 Liquid
濃    度 1mg/ml
免 疫 原 KLH conjugated Synthesised phosphopeptide derived from human Insulin Receptor around the phosphorylation site of Tyr999: PE(p-Y)LS 
亞    型 IgG
純化方法 affinity purified by Protein A
緩 沖 液 0.01M TBS (pH7.4) with 1% BSA, 0.02% Proclin300 and 50% Glycerol.
保存條件 Shipped at 4℃. Store at -20℃ for one year. Avoid repeated freeze/thaw cycles.
注意事項 This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
PubMed PubMed
產(chǎn)品介紹 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]

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: 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.

Subunit:
Tetramer of 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains contribute to the formation of the ligand-binding domain, while the beta chains carry the kinase domain. Forms a hybrid receptor with IGF1R, the hybrid is a tetramer consisting of 1 alpha chain and 1 beta chain of INSR and 1 alpha chain and 1 beta chain of IGF1R. Interacts with SORBS1 but dissociates from it following insulin stimulation. Binds SH2B2. Activated form of INSR interacts (via Tyr-999) with the PTB/PID domains of IRS1 and SHC1. The sequences surrounding the phosphorylated NPXY motif contribute differentially to either IRS1 or SHC1 recognition. Interacts (via tyrosines in the C-terminus) with IRS2 (via PTB domain and 591-786 AA); the 591-786 would be the primary anchor of IRS2 to INSR while the PTB domain would have a stabilizing action on the interaction with INSR. Interacts with the SH2 domains of the 85 kDa regulatory subunit of PI3K (PIK3R1) in vitro, when autophosphorylated on tyrosine residues. Interacts with SOCS7. Interacts (via the phosphorylated Tyr-999), with SOCS3. Interacts (via the phosphorylated Tyr-1185, Tyr-1189, Tyr-1190) with SOCS1. Interacts with CAV2 (tyrosine-phosphorylated form); the interaction is increased with 'Tyr-27'phosphorylation of CAV2 (By similarity). Interacts with ARRB2 (By similarity). Interacts with GRB10; this interaction blocks the association between IRS1/IRS2 and INSR, significantly reduces insulin-stimulated tyrosine phosphorylation of IRS1 and IRS2 and thus decreases insulin signaling. Interacts with GRB7 (By similarity). Interacts with PDPK1. Interacts (via Tyr-1190) with GRB14 (via BPS domain); this interaction protects the tyrosines in the activation loop from dephosphorylation, but promotes dephosphorylation of Tyr-999, this results in decreased interaction with, and phosphorylation of, IRS1. Interacts (via subunit alpha) with ENPP1 (via 485-599 AA); this interaction blocks autophosphorylation. Interacts with PTPRE; this interaction is dependent of Tyr-1185, Tyr-1189 and Tyr-1190 of the INSR. Interacts with STAT5B (via SH2 domain). Interacts with PTPRF.

Subcellular Location:
Cell membrane.

Tissue Specificity:
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 (at protein level). Overexpressed in several tumors, including breast, colon, lung, ovary, and thyroid carcinomas.

Post-translational modifications:
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.

DISEASE:
Rabson-Mendenhall syndrome Leprechaunism Diabetes mellitus, non-insulin-dependent Familial hyperinsulinemic hypoglycemia 5 Insulin-resistant diabetes mellitus with acanthosis nigricans type A.

Similarity:
Belongs to the protein kinase superfamily. Tyr protein kinase family.
Insulin receptor subfamily.
Contains 3 fibronectin type-III domains.
Contains 1 protein kinase domain.

SWISS:
P06213

Gene ID:
3643

Database links:

Entrez Gene: 3643 Human

Entrez Gene: 16337 Mouse

Entrez Gene: 24954 Rat

Omim: 147670 Human

SwissProt: P06213 Human

SwissProt: P15208 Mouse

SwissProt: P15127 Rat

Unigene: 465744 Human

Unigene: 268003 Mouse

Unigene: 9876 Rat



產(chǎn)品圖片
Sample: Lovo (Human)Cell Lysate at 40 ug HepG2 (Human) Cell Lysate at 40 ug Primary: Anti-p-IFNGR1 (Tyr457)(bs-16680R)at 1/300 dilution Secondary: IRDye800CW Goat Anti-RabbitIgG at 1/20000 dilution Predicted band size: 70kD Observed band size: 125kD
Paraformaldehyde-fixed, paraffin embedded (rat brain tissue); Antigen retrieval by boiling in sodium citrate buffer (pH6.0) for 15min; Block endogenous peroxidase by 3% hydrogen peroxide for 20 minutes; Blocking buffer (normal goat serum) at 37°C for 30min; Antibody incubation with (Insulin Receptor (Tyr999)) Polyclonal Antibody, Unconjugated (bs-16680R) at 1:400 overnight at 4°C, followed by operating according to SP Kit(Rabbit) (sp-0023) instructionsand DAB staining.
Blank control (blue line): HL60(fixed with 70% ethanol Overnight at 4℃). Primary Antibody (green line): Rabbit Anti-Phospho-Insulin Receptor (Tyr999)antibody (bs-16680R),Dilution: 0.2μg /10^6 cells; Isotype Control Antibody (orange line): Rabbit IgG . Secondary Antibody (white blue line): Goat anti-rabbit IgG-PE,Dilution: 1μg /test.
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