The insulin-like effects of vanadate are independent of the insulin receptor and insulin receptor substrate 1 (IRS-1) phosphorylation. A cytosolic protein tyrosine kinase (CytPTK), sensitive to inhibition by nanomolar concentrations of staurosporine (concentration at which 50% inhibition occurs [IC50], 1–2 nmol/1), has been implicated in some (i.e., glucose oxidation, lipogenesis) but not all (i.e., hexose uptake, inhibition of lipolysis) of the insulin-like effects of vanadate. We report here the existence of another nonreceptor protein tyrosine kinase in rat adipocytes, located exclusively in the plasma membranes (MembPTK), which we suggest is associated with hexose uptake and the antilipolytic activity of vanadate. MembPTK is a nong-lycoprotein with an estimated molecular weight of 55–60 kDa. In a cell-free experiment, vanadate activates MembPTK seven- to ninefold (median effective dose, 17 ± 2 μmol/l). Vanadate-activated MembPTK is inhibited by staurosporine (IC50, 60 ± 5 nmol/l). In intact adipocytes, staurosporine antagonized vanadate-induced hexose uptake (IC50, 6.0 ± 0.3 μmol/l) and significantly reversed the antilipolytic effect of vanadate (IC50, 5.0 ± 0.4 μmol/l). After vanadate treatment, a phosphorylated P55 protein is immunoprecipitated by antibodies to both phosphotyrosine and phosphatidyli-nositol (PI) 3-kinase. In conclusion, rat adipocytes contain an additional vanadate-activatable nonreceptor membranous protein tyrosine kinase that may participate in the effects of vanadate not carried out by CytPTK. We also suggest that after treatment with vanadate, MembPTK is activated by autophosphorylation and interacts with PI 3-kinase. This may explain how vanadate activates PI 3-kinase without involving receptor activation and IRS-1 phosphorylation.
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Original Articles|
November 01 1997
Vanadate Activates Membranous Nonreceptor Protein Tyrosine Kinase in Rat Adipocytes
Gerard Elberg;
Gerard Elberg
Department of Biochemistry, Weizmann Institute of Science
Rehovot, Israel
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Zhibin He;
Zhibin He
Department of Biochemistry, Weizmann Institute of Science
Rehovot, Israel
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Jinping Li;
Jinping Li
Department of Biochemistry, Weizmann Institute of Science
Rehovot, Israel
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Natesampillai Sekar;
Natesampillai Sekar
Department of Biochemistry, Weizmann Institute of Science
Rehovot, Israel
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Yoram Shechter
Yoram Shechter
Department of Biochemistry, Weizmann Institute of Science
Rehovot, Israel
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Address correspondence and reprint requests to Dr. Yoram Shechter, Department of Biochemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
Diabetes 1997;46(11):1684–1690
Article history
Received:
March 27 1997
Revision Received:
June 25 1997
Accepted:
June 25 1997
PubMed:
9356013
Citation
Gerard Elberg, Zhibin He, Jinping Li, Natesampillai Sekar, Yoram Shechter; Vanadate Activates Membranous Nonreceptor Protein Tyrosine Kinase in Rat Adipocytes. Diabetes 1 November 1997; 46 (11): 1684–1690. https://doi.org/10.2337/diab.46.11.1684
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