Evidence for the distinct vanadyl(+4)-dependent activating system for manifesting insulin-like effects.
Both exogenously added vanadate (oxidation state +5) and vanadyl (oxidation state +4) mimic the rapid responses of insulin through alternative signaling pathways, not involving insulin receptor activation [reviewed in Shechter et al. (1995) Mol. Cell. Biochem. 153, 39-47]. Vanadium exhibits complex chemistry, fluctuating between vanadate(+5) and vanadyl(+4), according to the prevailing conditions. Using several experimental approaches, we report here on a distinct vanadate(+5)-independent, vanadyl(+4)-dependent activating pathway. The key components of this pathway are membrane protein phosphotyrosine phosphatases (PTPases) and a cytosolic (nonreceptor) protein-tyrosine kinase (CytPTK). We further suggest that vanadate(+5) is not reduced rapidly to vanadyl(+4) inside the cell, and entered vanadyl sulfate(+4) is capable of undergoing spontaneous oxidation to vanadate(+5) in vivo. Finally, we show that the promotion and full expression of a downstream bioeffect such as lipogenesis requires both activation of CytPTK and prolonged stability of vanadyl(+4) against oxidation.
Li
J
J
Department of Biochemistry, Weizmann Institute of Science, Rehovot, Israel.
Elberg
G
G
Crans
D C
DC
Shechter
Y
Y
D017667:Adipocytes / Q000187:drug effects*; D000818:Animals; D003600:Cytosol / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005978:Glutathione / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D008055:Lipids / Q000096:biosynthesis; D008297:Male; D018716:Molecular Mimicry; D010084:Oxidation-Reduction; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D017968:Vanadium Compounds / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D017968:Vanadium Compounds; C034028:vanadyl sulfate; D011505:Protein-Tyrosine Kinases; D005978:Glutathione