Lactosylceramide alpha2,3-sialyltransferase is induced via a PKC/ERK/CREB-dependent pathway in K562 human leukemia cells.
Previously we showed that the human GM3 synthase gene was expressed during the induction of megakaryocytic differentiation in human leukemia K562 cells by phorbol 12-myristate 13-acetate (PMA). In this study we found that treatment of PMA-induced K562 cells with Gö6976, a specific inhibitor of PKC, and U0126, an inhibitor of the extracellular signal-regulated kinase (ERK) reduced expression of GM3 synthase, whereas wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K) did not. Moreover, activation of ERK and cAMP response element binding protein (CREB) was prevented by pretreatment with Gö6976 and U0126. PMA stimulated the promoter activity of the 5'-flanking region from -177 to -83 region of the GM3 synthase gene, and mutation or deletion of a CREB site located around -143 of the promoter reduced PMA-stimulated promoter activity, as did the inhibitors Gö6976 and U0126. Our results demonstrate that induction of GM3 synthase during megakaryocytic differentiation in PMA-stimulated human leukemia K562 cells depends upon the PKC/ERK/CREB pathway.
Choi
Hee-Jung
HJ
Molecular and Cellular Glycobiology Unit, Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, Korea.
Park
Young-Guk
YG
Kim
Cheorl-Ho
CH
D024506:5' Flanking Region; D000730:Androstadienes / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D020014:K562 Cells; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects; D009154:Mutation; D009439:Neuraminidase / Q000096:biosynthesis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000077191:Wortmannin
D000730:Androstadienes; D002227:Carbazoles; D017362:Cyclic AMP Response Element-Binding Protein; D048049:Extracellular Signal-Regulated MAP Kinases; D007211:Indoles; D009439:Neuraminidase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D012799:Sialyltransferases; D013755:Tetradecanoylphorbol Acetate; D000077191:Wortmannin; C115163:CREB1 protein, human; C081021:Go 6976; C021343:haematoside synthetase; C036052:GM3 ganglioside sialidase