| Abstract
| - Both exogenously added vanadate (oxidation state +5) and vanadyl(oxidation state +4) mimicthe rapid responses of insulin through alternative signalingpathways, not involving insulin receptoractivation [reviewed in Shechter et al. (1995) Mol.Cell. Biochem. 153, 39−47]. Vanadiumexhibitscomplex chemistry, fluctuating between vanadate(+5) andvanadyl(+4), according to the prevailingconditions. Using several experimental approaches, we report hereon a distinct vanadate(+5)-independent,vanadyl(+4)-dependent activating pathway. The keycomponents of this pathway are membrane proteinphosphotyrosine phosphatases (PTPases) and a cytosolic (nonreceptor)protein-tyrosine kinase (CytPTK).We further suggest that vanadate(+5) is not reduced rapidlyto vanadyl(+4) inside the cell, and enteredvanadyl sulfate(+4) is capable of undergoing spontaneousoxidation to vanadate(+5) in vivo.Finally,we show that the promotion and full expression of a downstreambioeffect such as lipogenesis requiresboth activation of CytPTK and prolonged stability of vanadyl(+4)against oxidation.
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