Interaction of Insulin-Like Growth Factor-Binding Protein 2 with α2-Macroglobulin in the Circulation

Abstract

Insulin-like growth factors (IGFs) play active role in mitogenic and metabolic processes. In the peripheral circulation, they are mostly bound to specific IGF-binding proteins (IGFBPs). Proteolysis of IGFBPs releases free, active IGFs. IGFBP-2 is the second most abundant of the six binding proteins and its concentration increases in catabolic states. The possible interaction between IGFBP-2 and other proteins in the circulation was investigated in this study. Our results showed that IGFBP-2 associates with α2-macroglobulin (α2M), a protease inhibitor. Formation of IGFBP-2/α2M complexes most likely contributes to the regulation of IGFBP-2 proteolysis and, thus, the activity of IGFs.

Remission of Diabetes Following Bariatric Surgery: Plasma Proteomic Profiles

“…Activation of A2M by proteases alters the interaction of A2M with these ligands and induces cell signaling [36]. A2M impacts in the transport and biological activity of insulin-like growth factors [37,38] and increased A2M serum levels, which characterize patients with diabetes [39,40].…”

Complexes between insulin-like growth factor binding proteins and alpha-2-macroglobulin in patients with tumor

“…1, entire profiles of immunoreactive IGFBP-1 and IGFBP-2 proteins are shown (fragment, monomer, dimer, higher oligomer, complex). Protein bands at approximately 200 kDa were previously discovered to be complexes with α2M (Šunderić et al, 2013;Westwood et al, 2001). Although the intention of this work was to study IGFBP/α2M complexes, both complexes (C) and monomer forms (M) of IGFBP-1 and IGFBP-2 are shown in Figs.…”

“…IGFBP-1 and IGFBP-2 were often found to increase in catabolic states at the expense of IGFBP-3, and cancer is one of them (Baxter, 2001). IGFBP-1 and IGFBP-2 express more similarity with each other than with the rest of IGFBPs, in terms of structural homology, ability to form only binary complexes with IGF molecules, possession of (Arg-Glu-Asp) RGD sequence which enables their interaction with cell surface integrin receptors (Chesik et al, 2010;Schütt et al, 2004) and ability to interact with alpha-2-macroglobulin (α2M) (Šunderić et al, 2013;Westwood et al, 2001). Processes in which these two IGFBPs are involved and mechanisms which control their synthesis are, however, completely different.…”

Insulin-like Growth Factor System and Aging

“…Alpha-2-macroglobulin (α2M) is the only protein binding with IGFBP2. Recent studies have found that α2M and IGFBP2 can form complex, but the physiological function of this phenomenon is not clear [39].…”