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 IGF1R/CD221/IGF-I R  蛋白

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IGF1R/CD221/IGF-I R 相关研究领域

IGF1R/CD221/IGF-I R 相關信號通路

IGF1R/CD221/IGF-I R 相關蛋白、抗體、cDNA基因、ELISA試劑盒

IGF1R/CD221/IGF-I R 相關蛋白、抗體、cDNA基因、ELISA試劑盒

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IGF1R/CD221/IGF-I R 概述&蛋白信息

IGF1R/CD221/IGF-I R 相關資訊

IGF1R/CD221/IGF-I R 研究背景

基因概述: This receptor binds insulin-like growth factor with a high affinity. It has tyrosine kinase activity. The IGF1R plays a critical role in transformation events. Cleavage of the precursor generates alpha and beta subunits. IGF1R is highly overexpressed in most malignant tissues where it functions as an anti-apoptotic agent by enhancing cell survival.
General information above from NCBI
催化活性: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. {ECO:0000255|PROSITE-ProRule:PRU10028, ECO:0000269|PubMed:11694888, ECO:0000269|PubMed:17317169, ECO:0000269|PubMed:18566589, ECO:0000269|PubMed:19041240, ECO:0000269|PubMed:19778024, ECO:0000269|PubMed:20675137, ECO:0000269|PubMed:21414779, ECO:0000269|PubMed:21441024, ECO:0000269|PubMed:7679099, ECO:0000269|Ref.50}.
酶調控: ENZYME REGULATION: Activated by autophosphorylation at Tyr-1165, Tyr-1161 and Tyr-1166 on the kinase activation loop; phosphorylation at all three tyrosine residues is required for optimal kinase activity. Inhibited by MSC1609119A-1, BMS-754807, PQIP, benzimidazole pyridinone, isoquinolinedione, bis-azaindole, 3-cyanoquinoline, 2,4-bis-arylamino-1,3-pyrimidine, pyrrolopyrimidine, pyrrole-5-carboxaldehyde, picropodophyllin (PPP), tyrphostin derivatives. While most inhibitors bind to the ATP binding pocket, MSC1609119A-1 functions as allosteric inhibitor and binds close to the DFG motif and the activation loop. {ECO:0000269|PubMed:11694888, ECO:0000269|PubMed:14729630, ECO:0000269|PubMed:17317169, ECO:0000269|PubMed:18566589, ECO:0000269|PubMed:19041240, ECO:0000269|PubMed:19778024, ECO:0000269|PubMed:20545947, ECO:0000269|PubMed:20675137, ECO:0000269|PubMed:21414779, ECO:0000269|PubMed:21441024, ECO:0000269|Ref.50}.
亞單位結構: 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 chain carries the kinase domain. Interacts with PIK3R1 and with the PTB/PID domains of IRS1 and SHC1 in vitro when autophosphorylated on tyrosine residues. Forms a hybrid receptor with INSR, 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 ARRB1 and ARRB2. Interacts with GRB10. Interacts with GNB2L1/RACK1. Interacts with SOCS1, SOCS2 and SOCS3. Interacts with 14-3-3 proteins. Interacts with NMD2. Interacts with MAP3K5. Interacts with STAT3. {ECO:0000269|PubMed:10454568, ECO:0000269|PubMed:11071852, ECO:0000269|PubMed:11591350, ECO:0000269|PubMed:11694888, ECO:0000269|PubMed:11884618, ECO:0000269|PubMed:12556535, ECO:0000269|PubMed:12821780, ECO:0000269|PubMed:15878855, ECO:0000269|PubMed:15998644, ECO:0000269|PubMed:17317169, ECO:0000269|PubMed:1846292, ECO:0000269|PubMed:18566589, ECO:0000269|PubMed:19041240, ECO:0000269|PubMed:19778024, ECO:0000269|PubMed:20545947, ECO:0000269|PubMed:21414779, ECO:0000269|PubMed:21441024, ECO:0000269|PubMed:7541045, ECO:0000269|PubMed:9581554, ECO:0000269|PubMed:9727029, ECO:0000269|PubMed:9822622, ECO:0000269|Ref.50}.
亞細胞定位: Cell membrane {ECO:0000269|PubMed:17524361}; Single-pass type I membrane protein {ECO:0000269|PubMed:17524361}.
組織特異性: Found as a hybrid receptor with INSR in muscle, heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibroblasts, spleen and placenta (at protein level). Expressed in a variety of tissues. Overexpressed in tumors, including melanomas, cancers of the colon, pancreas prostate and kidney. {ECO:0000269|PubMed:12019176, ECO:0000269|PubMed:8247543, ECO:0000269|PubMed:9202395, ECO:0000269|PubMed:9355755}.
翻譯後修飾: Autophosphorylated on tyrosine residues in response to ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Autophosphorylation occurs in a sequential manner; Tyr-1165 is predominantly phosphorylated first, followed by phosphorylation of Tyr-1161 and Tyr-1166. While every single phosphorylation increases kinase activity, all three tyrosine residues in the kinase activation loop (Tyr-1165, Tyr-1161 and Tyr-1166) have to be phosphorylated for optimal activity. Can be autophosphorylated at additional tyrosine residues (in vitro). Autophosphorylated is followed by phosphorylation of juxtamembrane tyrosines and C-terminal serines. Phosphorylation of Tyr-980 is required for IRS1- and SHC1-binding. Phosphorylation of Ser-1278 by GSK-3beta restrains kinase activity and promotes cell surface expression, it requires a priming phosphorylation at Ser-1282. Dephosphorylated by PTPN1 (By similarity). {ECO:0000250}.; Polyubiquitinated at Lys-1168 and Lys-1171 through both 'Lys-48' and 'Lys-29' linkages, promoting receptor endocytosis and subsequent degradation by the proteasome. Ubiquitination is facilitated by pre-existing phosphorylation. {ECO:0000269|PubMed:11694888, ECO:0000269|PubMed:12821780, ECO:0000269|PubMed:18501599, ECO:0000269|PubMed:19041240, ECO:0000269|PubMed:21994939, ECO:0000269|PubMed:7541045}.; Sumoylated with SUMO1. {ECO:0000269|PubMed:20596523}.; Controlled by regulated intramembrane proteolysis (RIP). Undergoes metalloprotease-dependent constitutive ectodomain shedding to produce a membrane-anchored 52 kDa C-Terminal fragment which is further processed by presenilin gamma-secretase to yield an intracellular 50 kDa fragment. {ECO:0000269|PubMed:17524361}.
相關疾病 : DISEASE: Insulin-like growth factor 1 resistance (IGF1RES) [MIM:270450]: A disorder characterized by intrauterine growth retardation, poor postnatal growth and increased plasma IGF1 levels. {ECO:0000269|PubMed:14657428, ECO:0000269|PubMed:15928254}. Note=The disease is caused by mutations affecting the gene represented in this entry.
相似的序列: Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.; Contains 4 fibronectin type-III domains. {ECO:0000255|PROSITE-ProRule:PRU00316}.; Contains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
General information above from UniProt

The insulin-like growth factor-1 receptor (IGF1R) is a transmembrane tyrosine kinase involved in several biological processes including cell proliferation, differentiation, DNA repair, and cell survival. This a disulfide-linked heterotetrameric transmembrane protein consisting of two α and two β subunits, and among which, the α subunit is extracellular while the β subunit has an extracellular domain, a transmembrane domain and a cytoplasmic tyrosine kinase domain. IGF1R signalling pathway is activated in the mammalian nervous system from early developmental stages. Its major effect on developing neural cells is to promote their growth and survival. This pathway can integrate its action with signalling pathways of growth and morphogenetic factors that induce cell fate specification and selective expansion of specified neural cell subsets. Modulation of cell migration is another possible role that IGF1R activation may play in neurogenesis. In the mature brain, IGF-I binding sites have been found in different regions of the brain, and multiple reports confirmed a strong neuroprotective action of the IGF-IR against different pro-apoptotic insults. IGF1R is an important signaling molecule in cancer cells and plays an essential role in the establishment and maintenance of the transformed phenotype. Inhibition of IGF1R signaling thus appears to be a promising strategy to interfere with the growth and survival of cancer cells. IGF1R is frequently overexpressed by tumours, and mediates proliferation and apoptosis protection. IGF signalling also influences hypoxia signalling, protease secretion, tumour cell motility and adhesion, and thus can affect the propensity for invasion and metastasis. Therefore, the IGF1R is now an attractive anti-cancer treatment target.

Immune Checkpoint   Immunotherapy   Cancer Immunotherapy   Targeted Therapy

IGF1R/CD221/IGF-I R 別稱

IGFR,CD221,IGFIR,JTK13, [homo-sapiens]
CD221,IGF1R,IGFIR,JTK13,MGC142170,MGC142172,MGC18216, [human]
A330103N21Rik,CD221,D930020L01,hyft,Igf1r,IGF-1R, [mouse]
hyft,CD221,IGF-1R,D930020L01,A330103N21Rik, [mus-musculus]

IGF1R/CD221/IGF-I R 相關文獻

  • Bhr C, et al. (2004) The insulin like growth factor-1 receptor (IGF-1R) as a drug target: novel approaches to cancer therapy. Growth Horm IGF Res. 14 (4): 287-95.
  • Riedemann J, et al. (2006) IGF1R signalling and its inhibition. Endocr Relat Cancer. 13 Suppl 1: 33-43.
  • Gualco E, et al. (2009) IGF-IR in neuroprotection and brain tumors. Front Biosci. 14: 352-75.
  • Annenkov A. (2009) The insulin-like growth factor (IGF) receptor type 1 (IGF1R) as an essential component of the signalling network regulating neurogenesis. Mol Neurobiol. 40 (3): 195-215.
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