IGF1R Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R. When present in a hybrid receptor with INSR, 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. Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily. 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. Note: This description may include information from UniProtKB.
Protein type: EC 2.7.10.1; InsR family; Kinase, protein; Membrane protein, integral; Protein kinase, TK; Protein kinase, tyrosine (receptor); TK group
Chromosomal Location of Human Ortholog: 1q22
Cellular Component:  alphav-beta3 integrin-IGF-1-IGF1R complex; axon; caveola; cytoplasm; insulin receptor complex; integral component of membrane; integral component of plasma membrane; intracellular membrane-bounded organelle; membrane; neuron projection; neuronal cell body; nucleus; plasma membrane; receptor complex; T-tubule
Molecular Function:  ATP binding; G-protein alpha-subunit binding; identical protein binding; insulin binding; insulin receptor binding; insulin receptor substrate binding; insulin-activated receptor activity; insulin-like growth factor binding; insulin-like growth factor I binding; insulin-like growth factor-activated receptor activity; phosphatidylinositol 3-kinase binding; protein binding; protein tyrosine kinase activity; transmembrane receptor protein tyrosine kinase activity
Biological Process:  adrenal gland development; aging; amyloid-beta clearance; anatomical structure development; animal organ morphogenesis; axonogenesis; brain development; cardiac atrium development; cellular response to aldosterone; cellular response to amyloid-beta; cellular response to angiotensin; cellular response to dexamethasone stimulus; cellular response to estradiol stimulus; cellular response to glucose stimulus; cellular response to insulin stimulus; cellular response to insulin-like growth factor stimulus; cellular response to mechanical stimulus; cellular response to progesterone stimulus; cellular response to testosterone stimulus; cellular response to transforming growth factor beta stimulus; cellular senescence; cerebellum development; dendritic spine maintenance; epidermis development; establishment of cell polarity; estrous cycle; exocrine pancreas development; glucose homeostasis; hippocampus development; immune response; inactivation of MAPKK activity; insulin receptor signaling pathway; insulin-like growth factor receptor signaling pathway; male sex determination; mammary gland development; negative regulation of apoptotic process; negative regulation of cholangiocyte apoptotic process; negative regulation of DNA-binding transcription factor activity; negative regulation of hepatocyte apoptotic process; negative regulation of MAPK cascade; negative regulation of muscle cell apoptotic process; negative regulation of protein kinase B signaling; neuron projection development; peptidyl-tyrosine autophosphorylation; peptidyl-tyrosine phosphorylation; phosphatidylinositol-mediated signaling; positive regulation of axon regeneration; positive regulation of cell migration; positive regulation of cell proliferation; positive regulation of cold-induced thermogenesis; positive regulation of cytokinesis; positive regulation of DNA metabolic process; positive regulation of MAPK cascade; positive regulation of meiotic cell cycle; positive regulation of mitotic nuclear division; positive regulation of osteoblast proliferation; positive regulation of phosphatidylinositol 3-kinase signaling; positive regulation of protein complex disassembly; positive regulation of protein kinase B signaling; positive regulation of smooth muscle cell proliferation; positive regulation of steroid hormone biosynthetic process; positive regulation of transcription, DNA-templated; prostate gland epithelium morphogenesis; protein autophosphorylation; protein heterooligomerization; protein phosphorylation; protein tetramerization; regulation of JNK cascade; response to ethanol; response to insulin; response to L-glutamate; response to nicotine; response to nutrient levels; response to vitamin E; transmembrane receptor protein tyrosine kinase signaling pathway
Reference #:  P24062 (UniProtKB)
Alt. Names/Synonyms: IGF-I receptor; Igf1r; IGFIRC; Insulin-like growth factor 1 receptor; Insulin-like growth factor 1 receptor alpha chain; Insulin-like growth factor 1 receptor beta chain; Insulin-like growth factor I receptor; JTK13
Gene Symbols: Igf1r
Molecular weight: 155,396 Da
Basal Isoelectric point: 5.57  Predict pI for various phosphorylation states
CST Pathways:  Angiogenesis  |  ESC Pluripotency and Differentiation  |  Tyrosine Kinases & Substrates
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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IGF1R

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Cross-references to other databases:  STRING  |  Reactome  |  BioGPS  |  Pfam  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene