For Research Use Only

 

Summary:

IGFBP-3 is the most abundant IGF-binding protein, accounting for as much as 75 or more of the circulating IGF-binding capacity in healthy subjects. IGFBP-3 shares functional properties with IGFBP-5 in that both peptides are able to form high molecular weight ternary complexes of ~150 kDa with ALS and either IGF-I or –II. However, IGFBP-5 circulates in much lower concentrations than IGFBP-3, and in healthy subjects the ternary complexes carry as much as 90 of IGFBP-3 but only about 50 of IGFBP-5.

Originally, the IGFBPs were thought to serve as IGF-carrier proteins, stabilizing plasma IGF levels and controlling the egress of IGF from the circulation to the extra-vascular compartment. Furthermore, it was assumed that IGFBP-complexed IGF was more or less biologically inactive, being deprived of its ability to interact with the IGF-I receptor. However, it soon became apparent that in some experimental settings the IGFBPs stimulated rather than inhibited IGF-I mediated actions, and accordingly, the IGFBPs are now often referred to as modulators of IGF-I bioactivity. In addition, the majority of the IGFBPs, and in particular IGFBP-3, exert IGF-I and IGF-I receptor independent effects, possible involving interactions with specific receptors located at the cell surface and intracellularly. For example, IGFBP-3 is nowadays considered to serve as an anticancer molecule, apparently protecting against several common cancers, and effects of IGFBP-3 on insulin signaling in cultured adipocytes have also been suggested.