IGF1R - Insulin-like growth factor 1 receptor - human protein (Function)
 
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IGF1R »  Insulin-like growth factor 1 receptor   [ EC 2.7.10.1 ]
 
Protein also known as:  Insulin-like growth factor I receptor (IGF-I receptor); CD antigen CD221. Cleaved into:  Insulin-like growth factor 1 receptor alpha chain; Insulin-like growth factor 1 receptor beta chain.
Gene name:  IGF1R
Entry whose protein(s) existence is based on evidence at protein level
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1 228 1
GENE REF ISO

Function

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Overview 
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.  
1
  • UniProtKB
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.  
1
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
G-protein alpha-subunit bindingdefinition[GO:0001965] silver  
1
  • Ortholog Compara
Identical protein bindingdefinition[GO:0042802]  
2
  • IntAct
Insulin bindingdefinition[GO:0043559]  
1
  • BHF-UCL
Insulin receptor bindingdefinition[GO:0005158]  
1
  • BHF-UCL
Insulin receptor substrate bindingdefinition[GO:0043560]  
1
  • UniProtKB
Insulin-like growth factor bindingdefinition[GO:0005520]  
2
  • UniProtKB
Insulin-like growth factor I bindingdefinition[GO:0031994]  
1
  • BHF-UCL
Insulin-like growth factor-activated receptor activitydefinition[GO:0005010]  
1
  • UniProtKB
Phosphatidylinositol 3-kinase bindingdefinition[GO:0043548]  
1
  • UniProtKB
Protein bindingdefinition[GO:0005515]  
22
  • IntAct
  • UniProtKB
Protein tyrosine kinase activitydefinition[GO:0004713]  
2
  • UniProtKB
GO biological process 
Axonogenesisdefinition[GO:0007409] silver  
1
  • Ortholog Compara
Brain developmentdefinition[GO:0007420] silver  
1
  • Ortholog Compara
Epidermis developmentdefinition[GO:0008544] silver  
1
  • Ortholog Compara
Establishment of cell polaritydefinition[GO:0030010] silver  
1
  • Ortholog Compara
Exocrine pancreas developmentdefinition[GO:0031017] silver  
1
  • Ortholog Compara
Immune responsedefinition[GO:0006955]  
1
  • BHF-UCL
Inactivation of MAPKK activitydefinition[GO:0051389]  
1
  • UniProtKB
Insulin receptor signaling pathwaydefinition[GO:0008286]  
1
  • PINC
Insulin-like growth factor receptor signaling pathwaydefinition[GO:0048009]  
1
  • UniProtKB
Male sex determinationdefinition[GO:0030238] silver  
1
  • Ortholog Compara
Mammary gland developmentdefinition[GO:0030879] silver  
1
  • Ortholog Compara
Negative regulation of apoptotic processdefinition[GO:0043066]  
1
  • UniProtKB
Negative regulation of muscle cell apoptotic processdefinition[GO:0010656] silver  
1
  • Ortholog Compara
Negative regulation of protein kinase B signalingdefinition[GO:0051898] silver  
1
  • Ortholog Compara
Negative regulation of sequence-specific DNA binding transcription factor activitydefinition[GO:0043433] silver  
1
  • Ortholog Compara
Peptidyl-tyrosine autophosphorylationdefinition[GO:0038083]  
1
  • MGI
Phosphatidylinositol 3-kinase signalingdefinition[GO:0014065]  
1
  • BHF-UCL
Phosphatidylinositol-mediated signalingdefinition[GO:0048015]  
1
  • BHF-UCL
Positive regulation of cell migrationdefinition[GO:0030335]  
1
  • BHF-UCL
Positive regulation of cell proliferationdefinition[GO:0008284]  
1
  • PINC
Positive regulation of cytokinesisdefinition[GO:0032467] silver  
1
  • Ortholog Compara
Positive regulation of DNA replicationdefinition[GO:0045740]  
1
  • BHF-UCL
Positive regulation of MAPK cascadedefinition[GO:0043410] silver  
1
  • Ortholog Compara
Positive regulation of mitosisdefinition[GO:0045840] silver  
1
  • Ortholog Compara
Positive regulation of protein kinase B signalingdefinition[GO:0051897] silver  
1
  • Ortholog Compara
Positive regulation of steroid hormone biosynthetic processdefinition[GO:0090031] silver  
1
  • Ortholog Compara
Prostate gland epithelium morphogenesisdefinition[GO:0060740] silver  
1
  • Ortholog Compara
Protein autophosphorylationdefinition[GO:0046777]  
3
  • UniProtKB
Protein heterooligomerizationdefinition[GO:0051291] silver  
1
  • Ortholog Compara
Protein tetramerizationdefinition[GO:0051262]  
1
  • UniProtKB
Regulation of JNK cascadedefinition[GO:0046328]  
1
  • UniProtKB
Response to vitamin Edefinition[GO:0033197] silver  
1
  • Ortholog Compara
Signal transductiondefinition[GO:0007165]  
1
  • PINC
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.10.1: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
11
  • UniProtKB
  • PROSITE-ProRule
It is regulated in the following manner
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.  
11
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Adherens junction  hsa04520+3480  
Endocytosis  hsa04144+3480  
Focal adhesion  hsa04510+3480  
Glioma  hsa05214+3480  
Long-term depression  hsa04730+3480  
Melanoma  hsa05218+3480  
Oocyte meiosis  hsa04114+3480  
Pathways in cancer  hsa05200+3480  
Progesterone-mediated oocyte maturation  hsa04914+3480  
Prostate cancer  hsa05215+3480  
According to Reactome, this protein belongs to the following pathways:
IRS-related events triggered by IGF1R  REACT_150203  
SHC-related events triggered by IGF1R  REACT_150139  
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)  REACT_150359  
 

Keywords

Molecular function 
Kinase  definition   [KW-0418]
Receptor  definition   [KW-0675]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: Insulin-like_growth_factor_1_receptor
GenomeRNAi: 3480
PRO: PR:P08069
Chemistry
GuidetoPHARMACOLOGY: 1801