Enhancement of insulin action by bis(acetylacetonato)oxovanadium(IV) occurs through uncompetitive inhibition of protein tyrosine phosphatase-1B
Makinen, MW; Rivera, SE; Zhou, KI; Brady, MJ
Published in: ACS Symposium Series
We have examined the influence of bis(acetylacetonato)oxovanadium(IV) [VO(acac)2] on the catalytic activity of protein tyrosine phosphatase-IB (PTPlB). In the presence of p-nitrophenylphosphate as the substrate, VO(acac)2 exhibited mixed inhibition. However, VO(acac)2 exhibited uncompetitive inhibition of the enzyme with the undecapeptide substrate DADEpYLIPQQG, in which the sequence corresponds to residues 988-998 of the epidermal growth factor receptor and pY indicates the phosphotyrosine residue. These results are consistent with our earlier observations, on the basis of phosphotyrosine immunoblots, showing that VO(acac)2 potentiates tyrosine phosphorylation of the insulin receptor synergistically with insulin. Because uncompetitive inhibitors of PTP1B have not been described heretofore, we discuss the importance of uncompetitive inhibition with respect to design of inhibitors of the enzyme for therapeutic purposes. © 2007 American Chemical Society.
