Phosphatidylinositol 3-kinase activity in murine erythroleukemia cells during DMSO-induced differentiation.
We have used murine erythroleukemia cells (MEL cells) to investigate the role of phosphatidylinositol 3-kinase (PI 3-kinase) in erythroid differentiation. When treated with dimethyl sulfoxide (DMSO), MEL cells grown on a fibronectin matrix become committed to erythroid differentiation asynchronously, with 90% of cells becoming committed by Day 3 of treatment. We found that during the first 3 days of DMSO treatment MEL cells showed a twofold increase in total PI 3-kinase activity and a fourfold increase in the highly phosphorylated PI 3-kinase product, PIP3. At the same time there was no change in the content of p85, the PI 3-kinase regulatory subunit. After Day 3, PI 3-kinase activity declined, in parallel with a disappearance of p85 antigen from the cells. Inclusion of the PI 3-kinase inhibitor Wortmannin in the culture medium resulted in an inhibition of cellular PI 3-kinase activity and a delay in DMSO-induced erythroid differentiation. These data suggest that PI 3-kinase may play a critical role during commitment of MEL cells to erythroid differentiation.
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Department of Biomedical Research, St. Elizabeth's Medical Center, Boston, Massachusetts 02135, USA.
Misra
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Susa
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Varticovski
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Cohen
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D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D000077191:Wortmannin
D000730:Androstadienes; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D000077191:Wortmannin; D004121:Dimethyl Sulfoxide