Aliases for IGF1R Gene
External Ids for IGF1R 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]
GeneCards Summary for IGF1R Gene
IGF1R (Insulin-Like Growth Factor 1 Receptor) is a Protein Coding gene. Diseases associated with IGF1R include insulin-like growth factor i and insulin-like growth factor 1 resistance to. Among its related pathways are PI3K-Akt signaling pathway and Glioma. GO annotations related to this gene include identical protein binding and insulin receptor binding. An important paralog of this gene is ALK.
UniProtKB/Swiss-Prot for IGF1R Gene
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
Insulin receptors (IRs) and insulin-like growth factor receptors (IGFRs) are formed from two subunits, each of which is comprised of an extracellular alpha-subunit and a transmembrane beta-subunit with intracellular tyrosine kinase activity. IR homodimers are activated by insulin and in adults, mediate an increase in glucose uptake through upregulation of Glut4 expression. Two isoforms of the IR exist; fetal IR-A and adult IR-B. IGF1R homodimers are activated by IGF-I and IGF-II and mediate pre- and postnatal growth. IGF2R sequesters IGF-II and acts to regulate its levels. IR-IGF1R heterodimers exist and, like IGF1R homodimers, are activated by IGF-I and IGF-II. IRs and IGFRs mediate their intracellular actions through the PI 3-K and RAS/RAF/MAPK signaling pathways and downstream effectors include mTOR, p70 S6 kinase, ERK and JNK. Many tumors have altered expression of IGF1R and its ligands and this constitutes an early, possible initiating, event in tumorigenesis. Decreases in IR signaling causing insulin resistance is a major component in the development of type 2 diabetes and congenital mutations in the IR can cause the fatal Donohue syndrome.