Insulin Like Growth Factor I Receptor (IGF-Ir) (IGF1R) Antibody – Mouse Monoclonal

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]

Function: This receptor binds insulin-like growth factor 1 (IGF1) with a high affinity and IGF2 with a lower affinity. It has a tyrosine-protein kinase activity, which is necessary for the activation of the IGF1-stimulated downstream signaling cascade. When present in a hybrid receptor with INSR, binds IGF1. Ref.19 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, Ref.22 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. Ref.7 Ref.10 Ref.11 Ref.12 Ref.19 Ref.22

Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.12

Cofactor: Manganese.

Enzyme regulation: Autophosphorylation activates the kinase activity. Ref.9

Subunit structure: 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. Forms a hybrid receptor with INSR, the hybrid is a tetramer consisting of 1 alpha chain and 1 beta chain of INSR and 1 alpha chain and 1 beta chain of IGF1R. Interacts with ARRB1 and ARRB2. Interacts with GRB10. Interacts with GNB2L1/RACK1. Ref.10 Ref.13 Ref.16 Ref.17 Ref.20 Ref.21

Subcellular location: Membrane; Single-pass type I membrane protein.

Tissue specificity: Found as a hybrid receptor with INSR in muscle, heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibroblasts, spleen and placenta (at protein level). Expressed in a variety of tissues. Ref.8 Ref.14 Ref.15

Post-translational modification: The cytoplasmic domain of the beta subunit is autophosphorylated on tyrosine residues in response to insulin-like growth factor I (IGF I). Ref.10 Ref.12 Ref.18 Ref.23 Ref.24 Ref.25 Ref.26Phosphorylation of Tyr-980 is required for IRS1- and SHC1-binding.

Involvement in disease: Defects in IGF1R are a cause of insulin-like growth factor 1 resistance (IGF1RES) [

MIM:270450]. It is a disorder characterized by intrauterine growth retardation and poor postnatal growth accompanied with increased plasma IGF1. Ref.27 Ref.28

Sequence similarities: Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.Contains 3 fibronectin type-III domains.Contains 1 protein kinase domain.

Sequence caution: The sequence BAG11657.1 differs from that shown. Reason: Erroneous initiation.