Endocrine Abstracts

The discovery that IGF binding proteins (IGFBPs) are capable of action independently of ligand binding opened up a broad scope of investigation into the mechanisms by which the IGFBPs elicit their intrinsic cellular effects. Numerous studies have demonstrated the special role of IGFBPs in as diverse processes as cell proliferation, migration and survival/apoptosis. However, the pathways by which these actions occur have not been completely defined but interactions of IGFBPs with other proteins or biomolecules must be involved.

IGFBPs can bind to many partners other than IGFs, although the relationship between most of these binding interactions and IGFBP actions remains uncertain. Several studies have identified membrane proteins that bind IGFBPs with relatively high affinity. These include proteins known to be involved in other signalling pathways (such as integrin receptor and TGFβ receptor) and putative receptors, the precise nature of which remains to be determined. Moreover, IGFBPs can also bind to intracellular (even nuclear) proteins.

Therefore, an exciting challenge in identifying the signalling pathways modulated by such interactions between IGFBPs and their partners is currently open.