IGF1R/CD221 (IGF1R) Active Protein

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]

IGF1R: a receptor tyrosine kinase that binds insulin-like growth factor 1 (IGF1) with a high affinity and IGF2 with a lower affinity. Functions as an anti-apoptotic agent by enhancing cell survival. Can play a critical role in transformation events. Cleavage of the precursor generates alpha and beta subunits. Tetramer of 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains contribute to the formation of the ligand- binding domain, while the beta chain carries the kinase domain. Interacts with PIK3R1 and with the PTB/PID domains of IRS1 and SHC1 in vitro when autophosphorylated on tyrosine residues. Mutated in rare cases of pre- and post-natal growth retardation. One SNP associated with increased human longevity. Increased expression of IGF1R and other pathway members associated with progression and malignancy in a range of cancers. Inhibitors: AG1024, AEW541.

Protein type: Kinase, protein; Protein kinase, TK; EC 2.7.10.1; Membrane protein, integral; Protein kinase, tyrosine (receptor); TK group; InsR family

Chromosomal Location of Human Ortholog: 15q26.3

Cellular Component: neuron projection; intracellular membrane-bound organelle; membrane; integral to plasma membrane; plasma membrane; caveola; receptor complex

Molecular Function: insulin binding; identical protein binding; insulin-like growth factor binding; protein binding; insulin-like growth factor I binding; insulin receptor substrate binding; protein-tyrosine kinase activity; phosphoinositide 3-kinase binding; G-protein alpha-subunit binding; insulin-like growth factor receptor activity; ATP binding; insulin receptor binding

Biological Process: phosphoinositide 3-kinase cascade; epidermis development; inactivation of MAPKK activity; protein heterooligomerization; protein amino acid autophosphorylation; exocrine pancreas development; signal transduction; regulation of JNK cascade; response to vitamin E; positive regulation of MAPKKK cascade; mammary gland development; male sex determination; positive regulation of cell proliferation; protein tetramerization; positive regulation of cytokinesis; negative regulation of protein kinase B signaling cascade; phosphoinositide-mediated signaling; positive regulation of mitosis; negative regulation of transcription factor activity; positive regulation of protein kinase B signaling cascade; insulin-like growth factor receptor signaling pathway; axonogenesis; establishment of cell polarity; insulin receptor signaling pathway; immune response; brain development; positive regulation of DNA replication; positive regulation of cell migration; negative regulation of apoptosis

Disease: Insulin-like Growth Factor I, Resistance To