Phosphatidylinositol-3-kinase activation and atypical protein kinase C zeta phosphorylation characterize the DMSO signalling in erythroleukemia cells.
Here we provide evidence for a role of phosphatidylinositol-3-kinase (PI-3-kinase) and for its product phosphatidylinositol-3,4, 5-triphosphate (PI3,4,5P3) in the occurrence of the metabolic differentiation state induced by DMSO in murine Friend erythroleukemia cells. Of note, the activation of PI-3-kinase correlated with the modulation of the activation of another enzyme, the atypical protein kinase C zeta (aPKC zeta). In particular, the expression of PI-3-kinase was substantially unaffected by DMSO treatment while its phosphorylation and the production of PI3,4,5P3 was strongly increased within 24 h of DMSO. Such a result was paralleled by an evident phosphorylation of a PKC zeta. Treatment of the cells with the two unrelated PI-3-kinase inhibitors wortmannin and LY 294002 impaired the recovery of the number of differentiated cells, therefore indicating that PI-3-kinase might be involved in the induction of erythroid differentiation, possibly engaging a protein kinase C zeta as downstream effector.
Cataldi
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Istituto di Morfologia Umana Normale, Facoltà di Medicina e Chirurgia, Universita' G. D'Annunzio, Via dei Vestini,6, 66100, Chieti, Italy. a.cataldi@morpho.unich.it
Di Pietro
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Centurione
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Grilli
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Cutroneo
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Miscia
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D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002867:Chromones / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000378:metabolism / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology*; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D008954:Models, Biological; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014407:Tumor Cells, Cultured; D000077191:Wortmannin; D000099221:Protein Kinase C zeta
D000730:Androstadienes; D002867:Chromones; D004121:Dimethyl Sulfoxide; D004791:Enzyme Inhibitors; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D000077191:Wortmannin; D000099221:Protein Kinase C zeta; C060974:phosphatidylinositol 3,4,5-triphosphate; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one