IGF-1R/CD221 Extracellular Domain (human, recombinant)

Insulin-like growth factor 1 receptor (IGF-1R), also known as CD221, is a member of the type II receptor tyrosine kinase family, previously known as the insulin receptor family.¹ It is synthesized as a preproreceptor with a signal peptide that is cleaved by a furin protease to produce an α- and a β-chain.² The mature protein forms homodimers, which are composed of two extracellular α-chain subunits that comprise the ligand-binding domain, a transmembrane domain, and two intracellular β-chain subunits that contain a tyrosine kinase domain and a C-terminal tail containing several phosphorylation sites located in two interactor domains, which are separated by a regulatory domain.^1,3 It is ubiquitously expressed and, when activated by its ligand IGF-1, IGF-1R undergoes autophosphorylation then phosphorylates and activates intracellular proteins, including insulin receptor substrate (IRS) proteins, activating downstream signaling via the PI3K/Akt, Rac, and RAS/RAF/MEK/ERK pathways.¹ Through these signaling pathways, IGF-1R is involved in inhibition of apoptosis and the regulation of cell migration and proliferation. Overexpression or mutation of CD221 is associated with a variety of cancers, and SNPs in CD221 are positively correlated with an increased risk of cancer.⁴ IGF-1R protein levels are increased in neurons of the temporal cortex in postmortem brain tissue from patients with Alzheimer’s disease, as well as around and within amyloid-β plaques.⁵ Increased levels of IGF-1R have been found in orbital fibroblasts, B cells, and T cells from patients with Graves' disease.⁶ Formulations containing anti-IGF-1R antibodies have been used in the treatment of Graves' orbitopathy. Cayman's IGF-1R/CD221 Extracellular Domain (human, recombinant) protein can be used for binding assays. This protein has calculated molecular weights of 81, 23, and 104 kDa for the α subunit, β subunit, and single chain of the receptor, respectively, and a predicted N-terminus of Glu31 after signal peptide cleavage. By SDS-PAGE, under reducing conditions, the apparent molecular masses are 120, 48, and 150 kDa, respectively, due to glycosylation.

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1. Delafontaine, P., Song, Y.-H., and Li, Y. Expression, regulation, and function of IGF-1, IGF-1R, and IGF-1 binding proteins in blood vessels. Arterioscler. Thromb. Vasc. Biol. 24(3), 435-444 (2004).

2. Adams, T.E., Epa, V.C., Garrett, T.P., et al. Structure and function of the type 1 insulin-like growth factor receptor. Cell. Mol. Life Sci. 57(7), 1050-1093 (2000).

3. Crudden, C., and Girnita, L. The tale of a tail: The secret behind IGF-1R’s oncogenic power. Sci. Signal. 13(633), eabb7887 (2020).

4. Wang, P., Mak, V.C.Y., and Cheung, L.W.T. Drugging IGF-1R in cancer: New insights and emerging opportunities. Genes Dis. (2022).

5. Moloney, A.M., Griffin, R.J., Timmons, S., et al. Defects in IGF-1 receptor, insulin receptor and IRS-½ in Alzheimer’s disease indicate possible resistance to IGF-1 and insulin signalling. Neurobiol. Aging 31(2), 224-243 (2010).

6. Smith, T.J., Huetwell, F.G.L., Hegedüs, L., et al. Role of IGF-1 pathway in the pathogenesis of Graves' orbitopathy. Best Pract. Res. Clin. Endocrinol. Metab. 26(3), 291-302 (2012).