======= IGF1R =======
== Gene Information ==
* **Official Symbol**: IGF1R
* **Official Name**: insulin like growth factor 1 receptor
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=3480|3480]]
* **UniProt**: [[https://www.uniprot.org/uniprot/P08069|P08069]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=IGF1R&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20IGF1R|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/147370|Open OMIM]]
== Function Summary ==
* **Entrez Summary**: This receptor binds insulin-like growth factor with a high affinity. It has tyrosine kinase activity. The insulin-like growth factor I receptor plays a critical role in transformation events. Cleavage of the precursor generates alpha and beta subunits. It is highly overexpressed in most malignant tissues where it functions as an anti-apoptotic agent by enhancing cell survival. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014].
* **UniProt Summary**: 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.
|Furin-like|
|Recep L domain|
|Pkinase|
|Pkinase Tyr|
|inactivation of MAPKK activity|
|insulin-like growth factor-activated receptor activity|
|insulin-activated receptor activity|
|alphav-beta3 integrin-IGF-1-IGF1R complex|
|insulin receptor complex|
|insulin binding|
|dendritic spine maintenance|
|insulin receptor substrate binding|
|insulin-like growth factor I binding|
|insulin-like growth factor receptor signaling pathway|
|insulin-like growth factor binding|
|phosphatidylinositol 3-kinase binding|
|amyloid-beta clearance|
|insulin receptor binding|
|dendritic spine organization|
|peptidyl-tyrosine autophosphorylation|
|phosphatidylinositol 3-kinase signaling|
|positive regulation of protein complex disassembly|
|cellular response to amyloid-beta|
|neuron projection organization|
|cellular component maintenance|
|response to amyloid-beta|
|transmembrane receptor protein tyrosine kinase activity|
|cellular response to glucose stimulus|
|phosphatidylinositol-mediated signaling|
|cellular response to hexose stimulus|
|cellular response to monosaccharide stimulus|
|inositol lipid-mediated signaling|
|cellular response to carbohydrate stimulus|
|positive regulation of phosphatidylinositol 3-kinase signaling|
|postsynapse organization|
|protein tyrosine kinase activity|
|insulin receptor signaling pathway|
|cellular glucose homeostasis|
|positive regulation of cold-induced thermogenesis|
|regulation of protein complex disassembly|
|regulation of phosphatidylinositol 3-kinase signaling|
|response to glucose|
|response to hexose|
|regulation of cold-induced thermogenesis|
|peptidyl-tyrosine phosphorylation|
|peptidyl-tyrosine modification|
|response to monosaccharide|
|protein tetramerization|
|cellular response to insulin stimulus|
|positive regulation of protein kinase B signaling|
|negative regulation of MAPK cascade|
|response to carbohydrate|
|glucose homeostasis|
|regulation of JNK cascade|
|carbohydrate homeostasis|
|protein autophosphorylation|
|receptor complex|
|regulation of protein kinase B signaling|
|negative regulation of protein kinase activity|
|response to insulin|
|regulation of stress-activated MAPK cascade|
|regulation of stress-activated protein kinase signaling cascade|
|negative regulation of kinase activity|
|cellular response to peptide hormone stimulus|
|synapse organization|
|negative regulation of transferase activity|
|axon|
|cellular response to peptide|
|regulation of MAP kinase activity|
|response to peptide hormone|
|negative regulation of protein phosphorylation|
|negative regulation of phosphorylation|
|response to peptide|
|positive regulation of cell migration|
|negative regulation of intracellular signal transduction|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|regulation of protein serine/threonine kinase activity|
|protein complex oligomerization|
|positive regulation of cell motility|
|positive regulation of cellular component movement|
|positive regulation of MAPK cascade|
|positive regulation of locomotion|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|negative regulation of protein modification process|
|cellular response to organonitrogen compound|
|cellular response to hormone stimulus|
|cellular response to nitrogen compound|
|intracellular membrane-bounded organelle|
|enzyme linked receptor protein signaling pathway|
|regulation of cellular response to stress|
|cellular chemical homeostasis|
|regulation of MAPK cascade|
|negative regulation of catalytic activity|
|regulation of protein kinase activity|
|regulation of cell migration|
|regulation of kinase activity|
|peptidyl-amino acid modification|
|negative regulation of apoptotic process|
|cellular homeostasis|
|negative regulation of programmed cell death|
|response to hormone|
|regulation of cell motility|
|positive regulation of cell population proliferation|
|protein phosphorylation|
|regulation of transferase activity|
|regulation of locomotion|
|regulation of cellular component movement|
|negative regulation of cell death|
|response to organonitrogen compound|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|negative regulation of cellular protein metabolic process|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|identical protein binding|
|response to nitrogen compound|
|negative regulation of protein metabolic process|
|chemical homeostasis|
|plasma membrane bounded cell projection organization|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|negative regulation of molecular function|
|cell projection organization|
|positive regulation of cellular component organization|
|cellular response to endogenous stimulus|
|positive regulation of protein modification process|
|negative regulation of signal transduction|
|phosphorylation|
|negative regulation of cell communication|
|negative regulation of signaling|
|integral component of plasma membrane|
|regulation of protein phosphorylation|
|response to endogenous stimulus|
|regulation of response to stress|
|ATP binding|
|regulation of apoptotic process|
|response to oxygen-containing compound|
|protein-containing complex assembly|
|regulation of programmed cell death|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|homeostatic process|
|positive regulation of signal transduction|
|regulation of cell death|
|intracellular signal transduction|
|positive regulation of protein metabolic process|
|positive regulation of multicellular organismal process|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|protein-containing complex subunit organization|
|immune response|
|membrane|
\\
=== CRISPR Data ===
^Screen^Score^
|[[:results:exp320|ABT-702 5μM plus CoCl2 18μM R07 exp320]]|-2.44|
|[[:results:exp38|Wortmannin 5μM R00 exp38]]|-2.14|
|[[:results:exp400|Senexin-A 25μM R07 exp400]]|-1.89|
|[[:results:exp343|Centrinone 0.5μM R07 exp343]]|-1.83|
|[[:results:exp128|GSK591 2.6μM R03 exp128]]|-1.77|
|[[:results:exp442|Ibrutinib 10μM R08 exp442]]|-1.72|
No correlation found to any other genes in chemogenomics.
Global Fraction of Cell Lines Where Essential: 14/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|2/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|1/20|
|lung|2/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|1/24|
|peripheral nervous system|0/16|
|plasma cell|2/15|
|prostate|1/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|1/29|
|uterus|0/5|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 3156
* **Expression level (log2 read counts)**: 6.65
{{:chemogenomics:nalm6 dist.png?nolink |}}