Lactosylceramide alpha2,3-sialyltransferase is induced via a PKC/ERK/CREB-dependent pathway in K562 human leukemia cells.

Abstract

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.

• Authors: Hee-Jung Choi, Young-Guk Park, Cheorl-Ho Kim
• Journal: Molecules and cells (Mol Cells) Vol. 23 Issue 2 Pg. 138-44 (Apr 30 2007) ISSN: 1016-8478 [Print] Korea (South)
• PMID: 17464189 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Androstadienes
• CREB1 protein, human
• Carbazoles
• Cyclic AMP Response Element-Binding Protein
• Indoles
• Phosphoinositide-3 Kinase Inhibitors
• Go 6976
• Sialyltransferases
• haematoside synthetase
• Protein Kinase C
• Extracellular Signal-Regulated MAP Kinases
• GM3 ganglioside sialidase
• Neuraminidase
• Tetradecanoylphorbol Acetate
• Wortmannin

Topics

• 5' Flanking Region
• Androstadienes (pharmacology)
• Carbazoles (pharmacology)
• Cell Differentiation (drug effects, physiology)
• Cyclic AMP Response Element-Binding Protein (metabolism)
• Enzyme Activation
• Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors, metabolism)
• Humans
• Indoles (pharmacology)
• K562 Cells
• Megakaryocytes (cytology, drug effects)
• Mutation
• Neuraminidase (biosynthesis)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Promoter Regions, Genetic
• Protein Kinase C (antagonists & inhibitors, metabolism)
• Sialyltransferases (genetics, metabolism)
• Signal Transduction
• Tetradecanoylphorbol Acetate (pharmacology)
• Wortmannin