IGF1R

Gene Information
 
Gene Symbol
IGF1R
 
Aliases
CD221, IGFIR, IGFR, JTK13
 
Entrez Gene ID
 
Gene Name
Insulin-like growth factor 1 receptor
 
Chromosomal Location
15q26.3
 
HGNC ID
 
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. (provided by RefSeq, Jul 2008)
 
GeneCards ID
 
UniGene
 
RefSeq DNA
 
RefSeq mRNA
  e!Ensembl
Gene
Transcript  
Protein

Gene Ontology (GO)

GO ID Ontology Definition Evidence Reference
GO:0006955 Biological process Immune response IMP 16886151
GO:0007165 Biological process Signal transduction TAS 3003744
GO:0008284 Biological process Positive regulation of cell proliferation TAS 10749889
GO:0008286 Biological process Insulin receptor signaling pathway TAS 10829031
GO:0014065 Biological process Phosphatidylinositol 3-kinase signaling IC 7541045
Protein Information
 
Protein Name
Insulin-like growth factor 1 receptor beta chain
 
Function
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
 
Refseq Proteins
 
UniProt
 
PDB
 
InterPro
 
Pfam
Pfam Accession Pfam ID
PF00041 fn3 Fibronectin type III domain
PF00757 Furin-like Furin-like cysteine rich region
PF01030 Recep_L_domain Receptor L domain
PF07714 Pkinase_Tyr Protein tyrosine kinase
 
KEGG
 
OMIM
 
Phenotype MIM ID

Associated Diseases

Diseases References
Acanthosis nigricans 9876344
Atherosclerotic plaque 17040964, 17600529, 11603921
Cancer (carcinoma) 14506643, 19500509, 10534157, 19174523, 8188079, 17233884, 15514114, 7491526, 12764580, 11943599, 17786320, 16297654, 19749460
Development delay 19864454
Hypertrophy 17940216, 8283604, 8573742, 14609609, 19665992, 17947802
   
References
 
Primary:
PMID: 7920895

Altered expression of insulin and insulin-like growth factor-I receptors in follicular and stromal compartments of polycystic ovaries.

Samoto T, Maruo T, Matsuo H, Katayama K, Barnea E R, Mochizuki M
Department of Obstetrics and Gynecology, Kobe University School of Medicine, Japan.
Endocr J. 1993 Aug;40(4):413-24.

Unreviewed Literature:

PubMed / PMC ID
Title Type of study
23457541, PMC3574134
The pancreas is altered by in utero androgen exposure: implications for clinical conditions such as polycystic ovary syndrome (PCOS). 
Clinical study 
23388061, PMC3724505
Insulin and insulin-like growth factor signaling increases proliferation and hyperplasia of the ovarian surface epithelium and decreases follicular integrity through upregulation of the PI3-kinase pathway. 
In vitro 
23141431
Metformin enhances the action of insulin on porcine granulosa-lutein cells in vitro. 
Effect of treatment 
22538004
In vivo oocyte IGF-1 priming increases inner cell mass proliferation of in vitro-formed bovine blastocysts. 
In vitro, animal studies 
21557698
Involvement of GDF-9, leptin, and IGF1 receptors associated with adipose tissue transplantation on fertility restoration in obese anovulatory mice. 
Animal study 

 

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