An interaction between inositol hexakisphosphate (IP6) and insulin-like growth factor II receptor binding sites in the rat brain.
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.
Douglas Hospital Research Center, Department of Psychiatry, McGill University, Montreal, Canada.
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D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D004705:Endocytosis; D006624:Hippocampus / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism* / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism*; D010833:Phytic Acid / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D017527:Receptor, IGF Type 2 / Q000378:metabolism* / Q000502:physiology; D011972:Receptor, Insulin / Q000378:metabolism
D033942:Adaptor Proteins, Vesicular Transport; D007328:Insulin; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D017527:Receptor, IGF Type 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D010833:Phytic Acid; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin