Recombinant Mouse IGF-I R/IGF1R Protein

The insulin-like growth factor I receptor (IGF-I R or IGF1R, designated CD221) is a 450 kDa disulfide‑linked heterotetrameric transmembrane glycoprotein consisting of two 130 kDa alpha and two 95 kDa beta subunits (1, 4). The IGF-1 R cDNA encodes a preproreceptor that is proteolytically cleaved to produce the extracellular alpha subunit (amino acid (aa) 31-737), which contains a cysteine-rich region and two ligand‑binding fibronectin type III (FN-III) domains, and the beta subunit (aa 742-1369), which contains an extracellular FN-III domain, transmembrane and cytoplasmic tyrosine kinase domains (1). Extracellular portions of mature mouse IGF-I R share 99.7% aa identity with rat, 96% with human, canine and porcine, and 95% with bovine and equine IGF-I R. IGF-I R is expressed in all cell types and tissues. It binds insulin-like growth factor I (IGF-I) with high affinity, IGF-II with lower affinity, and insulin with lowest affinity (2, 3). Both IGF-I R and the structurally similar insulin receptor (Ins R) activate the same signaling pathways in response to their respective ligands (3). IGF-I R/Ins R hybrids are formed in proportion to their expression and respond primarily to IGF-I, probably down‑regulating cellular response to insulin (2, 5). IGF signaling is also modulated by IGF binding proteins and the scavenger receptor, IGF-II R (4). Expression or glycosylation of IGF-I R may be altered in cancer cells (4, 5). Mice lacking IGF-I R show intrauterine growth deficiency and die at birth due to respiratory failure, and IGF-I R mutations in humans can retarded pre- and postnatal growth (6-8). IGF-I and its receptor are particularly important for neurogenesis, with deficiency producing microcephaly and learning disorders (9-11). Low expression of IGF-I R enhances lifespan in both mouse and human by increasing resistance to oxidative stress (12, 13).  IGF-I R expression in human embryonic stem cells is important for their survival and clonogenicity (14).