Recombinant Human IGFBP3

Insulin-like growth factor binding protein-3 (IGFBP-3) is one of six members of the insulinlike growth factor (IGF) binding protein superfamily which function to modulate the biological activity of IGF ^[1]. Human IGFBP-3 is the major binding protein of IGF where it exists in circulation as a ternary complex with the acid-labile subunit (ALS) ^[2]. Like other IGFBP members, human IGFBP-3 includes a cysteine-rich C-terminal domain, a highly variable central linker domain, and another N-terminal cysteine-rich domain ^{[2, 3]}. Human IGFBP-3 cDNA encodes a 291 amino acid (aa) precursor protein with a 27 aa signal peptide that is processed to generate the 264 aa mature protein. Mature human IGFBP-3 shares 82% aa sequence identity with both mouse and rat IGFBP-3. Post-translational glycosylation and phosphorylation of IGFBP-3 modifies the affinities of the binding protein. Proteolysis of IGFBP-3 by tissue plasminogen activator (tPA), a disintegrin and metaloproteases (ADAMs), and prostate specific antigen (PSA) contributes to IGFBP-3 degradation or a reduction in its affinity for IGF ^[4-6]. The majority of soluble IGFBP-3 found in circulation is secreted from hepatic non-parenchymal cells. IGFBP-3 expression can be modulated by p53 as well as by various cytokines and growth factors ^{[7, 8]}. In addition to its role in stabilizing and transporting circulating IGF, IGFBP-3 has been shown to potentiate EGF-EGFR-mediated cell growth through the activation of sphingosine kinase1 (SPHK1) and sphingosin-1-phosphate (S1P) ^{[9, 10]}. IGFBP-3 has also been shown to modulate adipogenesis ^[11]. Binding of IGFBP-3 to non-IGF-related ligands has been shown to regulate TGF-beta signaling, DNA damage, apoptosis, autophagy, and gene transcription ^[12].

Reference

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[2]. Baxter, R.C. (2013) J. Cell Commun. Signal 7:179.

[3]. Baxter, R.C. (2014) Nat. Rev. Cancer 14:329.

[4]. Mochizuki, S. et al. (2004) Biochem. Biophys. Res. Commun. 315:79.

[5]. Cohen, P. et al. (1994) J. Endocrinol. 142:407.

[6]. Bang, P. (1995) Prog. Growth Factor Res. 6:285

[7] Perks C.M. and J.M.Holly (2008) J. Mammary Gland Biol. Neoplasia 13:455.

[8]. Chan, K. and E.M. Spencer (1997) Endocrine 7:95.

[9]. Guix, M. et al. (2008) J. Clin. Invest. 118:2609.

[10]. Martin, J.L. et al. (2009) J. Biol. Chem. 284:25542.

[11]. Chan, S.S. et al. (2009) Am. J. Physiol. Endocrinol. Metab. 296:E654.

[12]. Martin, J.L. and R.C. Baxter (2011) Growth Factors 29:235.