An interaction between inositol hexakisphosphate (IP6) and insulin-like growth factor II receptor binding sites in...

Insulin-like growth factor II/mannose-6-phosphate (IGF II/Man-6-P) receptors participate in the trafficking of lysosomal enzymes and also in the transduction of the effects of the growth factor via transmembrane-anchored receptor protein. During ligand-induced endocytosis, this receptor interacts with clathrin-associated protein (AP-2) which can lead to their assembly and subsequent transport in coated vesicles to the lysosomes. Only recently has it been suggested that AP-2 itself may also act as one of the receptor sites for inositol hexakisphosphate (IP6). This evidence, together with autoradiographic data showing that [3H]IP6 binding sites in rat brain are similarly distributed to [125I] IGF II sites, led us to examine the possible interaction between IP6 and [125I]IGF II receptor binding sites using an autoradiographic approach. Our results indicate that IP6, at microM concentrations, competes for [125I]IGF II, but not [125I]IGF I or [125I]insulin binding sites in the rat brain. These results, in keeping with other evidence, suggest that IP6 may be able to regulate the [125I]IGF II receptor binding sites either directly or indirectly, possibly through clathrin-associated AP-2 sites.