An inositol phosphate glycan derived from a Trypanosoma brucei glycosyl phosphatidylinositol promotes protein dephosphorylation in rat epididymal adipocytes.
Some of the acute actions of insulin may be mediated by an enzyme-modulating inositol phosphate glycan, produced by the insulin-sensitive hydrolysis of a glycosyl phosphatidylinositol that is structurally similar to a membrane protein anchor. An inositol glycan fragment from the structurally characterized Trypanosoma brucei variant surface glycoprotein glycosyl phosphatidylinositol anchor inhibits isoproterenol-stimulated lipolysis in intact rat epididymal adipocytes in a manner mechanistically similar to that of insulin. To explore these effects in more detail, we evaluated the effects of this glycan on protein phosphorylation. Isoproterenol stimulates the phosphorylation of a 70-kilodalton (kDa) protein in these cells. Like insulin, the glycan fragment specifically attenuates the phosphorylation state of the phosphoprotein. In purified adipocyte cytosol, the glycan stimulates the dephosphorylation on serine residues of a 70-kDa protein in a time- and dose-dependent fashion. The glycan-dependent dephosphorylation of the 70-kDa phosphoprotein is unaffected by addition of trifluoroperazine, an inhibitor of serine/threonine phosphatase-2B, but is blocked by the addition of okadaic acid, an inhibitor of serine/threonine phosphatase-1 and -2A. The differential sensitivities of this dephosphorylation reaction to polycations, which activate phosphatase-2A, and phosphorylated inhibitor 1, which blocks phosphatase-1, suggest that dephosphorylation of the 70-kDa protein results from the specific activation of a type 1 serine/threonine phosphatase in adipocytes, providing a mechanistic basis for the insulin-mimetic effects of the inositol glycan.
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109.
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Misek
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Saltiel
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004988:Ethers, Cyclic / Q000494:pharmacology; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D019319:Okadaic Acid; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011134:Polysaccharides / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions; D014346:Trypanosoma brucei brucei / Q000737:chemistry / Q000378:metabolism*
D004988:Ethers, Cyclic; D017261:Glycosylphosphatidylinositols; D007295:Inositol Phosphates; D010750:Phosphoproteins; D011134:Polysaccharides; C028039:inositol phosphate glycan; D019319:Okadaic Acid; D007545:Isoproterenol