protein_function: Receptor tyrosine kinase which mediates actions ofinsulin-like growth factor 1 (IGF1). Binds IGF1 with high affinityand IGF2 and insulin (INS) with a lower affinity. The activatedIGF1R is involved in cell growth and survival control. IGF1R iscrucial for tumor transformation and survival of malignant cell.Ligand binding activates the receptor kinase, leading to receptorautophosphorylation, and tyrosines phosphorylation of multiplesubstrates, 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 twomain signaling pathways: the PI3K-AKT,PKB pathway and the Ras-MAPKpathway. The result of activating the MAPK pathway is increasedcellular proliferation, whereas activating the PI3K pathwayinhibits apoptosis and stimulates protein synthesis.Phosphorylated IRS1 can activate the 85 kDa regulatory subunit ofPI3K (PIK3R1), leading to activation of several downstreamsubstrates, including protein AKT,PKB. AKT phosphorylation, inturn, enhances protein synthesis through mTOR activation andtriggers the antiapoptotic effects of IGFIR throughphosphorylation and inactivation of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2,SOS by phosphorylated IRS1or Shc leads to recruitment of Ras and activation of the ras-MAPKpathway. In addition to these two main signaling pathways IGF1Rsignals also through the Janus kinase,signal transducer andactivator of transcription pathway (JAK,STAT). Phosphorylation ofJAK proteins can lead to phosphorylation,activation of signaltransducers and activators of transcription (STAT) proteins. Inparticular activation of STAT3, may be essential for thetransforming activity of IGF1R. The JAK,STAT pathway activatesgene transcription and may be responsible for the transformingactivity. JNK kinases can also be activated by the IGF1R. IGF1exerts inhibiting activities on JNK activation via phosphorylationand inhibition of MAP3K5,ASK1, which is able to directly associatewith the IGF1R.
IGF1R, also called IGFR or insulin-like growth factor 1 receptor, is a protein that found on the surface of human cells. This gene is mapped to 15q26.3. IGF1R belongs to the large class of tyrosine kinase receptors. This receptor mediates the effects of IGF-1, which is a polypeptide protein hormone similar in molecular structure to insulin. It plays an important role in growth and continues to have anabolic effects in adults - meaning that it can induce hypertrophy of skeletal muscle and other target tissues. IGF1R also plays a critical role in transformation events. It is highly overexpressed in most malignant tissues where it functions as an anti-apoptotic agent by enhancing cell survival.