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  3. IGF1R

IGF1R (Insulin like growth factor 1 receptor)

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Summary of IGF1R

IGF1R encodes for insulin growth factor receptors; overexpression can stop cell death by enhancing cell survival and is present in malignant tissues (R). 

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The Function of 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.

Protein names

Recommended name:

Insulin-like growth factor 1 receptor

Alternative name(s):

Insulin-like growth factor I receptor
IGF-I receptor
CD antigen CD221

IGF1R SNPs

    To see your genotype, you should be logged in and have a file with your genotype uploaded.

  1. RS2018860 (IGF1R) ??
  2. RS2229765 (IGF1R) ??
  3. RS2871865 (IGF1R) ??
  4. RS4966035 (IGF1R) ??
  5. RS6598541 (IGF1R) ??

Top Gene-Substance Interactions

IGF1R Interacts with These Diseases

Disease Score

Fixes

Methods to Increase IGF1R levels:

  • Increase intake of blueberries [R].

Substances That Increase IGF1R

Substances Interaction Organism Category

Substances That Decrease IGF1R

Substances Interaction Organism Category

Advanced Summary

IGF1R encodes for insulin growth factor receptors; overexpression can stop cell death by enhancing cell survival and is present in malignant tissues (R). 

     From NCBI Gene: Insulin-like growth factor 1 resistance toFrom UniProt: Insulin-like growth factor 1 resistance (IGF1RES): A disorder characterized by intrauterine growth retardation, poor postnatal growth and increased plasma IGF1 levels. [MIM:270450]

     From NCBI Gene: 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] From UniProt: 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 .

Conditions with Increased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Conditions with Decreased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Technical

The following transcription factors affect gene expression:

  • NF-kappaB
  • p53
  • NF-kappaB1
  • MEF-2A
  • Sp1
  • STAT1
  • STAT1beta
  • STAT1alpha

Tissue specificity:

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.

Gene Pathways:

  • Melanoma
  • Pathways in cancer
  • Signal Transduction
  • Adherens junction
  • Prostate cancer
  • Glioma
  • Long-term depression
  • Oocyte meiosis
  • Progesterone-mediated oocyte maturation

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.

Molecular Function:

  • Atp Binding
  • Insulin Binding
  • Insulin-Like Growth Factor-Activated Receptor Activity
  • Insulin-Like Growth Factor Binding
  • Insulin-Like Growth Factor I Binding
  • Insulin Receptor Binding
  • Insulin Receptor Substrate Binding
  • Phosphatidylinositol 3-Kinase Binding
  • Protein Tyrosine Kinase Activity
  • Identical Protein Binding

Biological Processes:

  • Immune Response
  • Inactivation Of Mapkk Activity
  • Insulin-Like Growth Factor Receptor Signaling Pathway
  • Insulin Receptor Signaling Pathway
  • Negative Regulation Of Apoptotic Process
  • Peptidyl-Tyrosine Autophosphorylation
  • Phosphatidylinositol 3-Kinase Signaling
  • Phosphatidylinositol-Mediated Signaling
  • Positive Regulation Of Cell Migration
  • Positive Regulation Of Cell Proliferation
  • Positive Regulation Of Dna Replication
  • Protein Autophosphorylation
  • Protein Tetramerization
  • Regulation Of Jnk Cascade
  • Signal Transduction

Drug Bank:

  • Insulin Regular
  • Insulin Lispro
  • Mecasermin
  • Insulin Glargine
*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

hypothetical protein| receptor tyrosine kinase| insulin-like growth factor 1 (somatomedin C)| A306_15486| AS27_12589| AS28_02086| CB1_000559011| CD221| D930020L01| EGK_17876| H920_16576| hyft| I79_011211| IGF1| igf-1r| IGF-1 receptor| IGF1 receptor| IGFIR| IGF-IR| IGFIRC| IGF-I receptor| IGFI receptor A| IGFR| IGFR1| IGF type I receptor Ia| insulin-like growth factor 1 receptor| insulin-like growth factor 1 receptor beta subunit| insulin like growth factor I receptor| insulin-like growth factor I receptor| insulin-like growth factor-I receptor| insulin-like growth factor receptor 1| insulin-like growth factor receptor I| insulin-like growth factor receptor type 1| insulin-like growth factor receptor tyrosine kinase| insulin-like growth factor type 1 receptor| JTK13| line 186| M91_03424| M959_10282| MDA_GLEAN10019504| N300_08534| N301_04410| N302_05024| N303_05971| N305_05585| N306_03914| N307_07517| N308_02631| N309_09380| N310_13282| N311_06465| N312_02267| N320_02465| N322_02630| N324_11399| N325_07040| N326_01934| N327_04701| N328_02454| N329_06390| N331_07412| N332_13686| N333_04495| N334_04505| N335_14024| N336_11404| N339_08482| N340_02808| N341_04010| PAL_GLEAN10007316| PANDA_011999| soluble IGF1R variant 1| soluble IGF1R variant 2| type 1 IGF receptor| type-I IGF receptor| tyrosine kinase| UY3_01083| xigf1r| xIGF-1R| xIGFR| XTK2| Y1Q_024038| Y956_09706| Z169_07687| igf1r

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