Lactosylceramide α2,3-Sialyltransferase Is Induced Via a PKC/ERK/CREB-dependent Pathway in K562 Human Leukemia Cells

  • Choi, Hee-Jung (Molecular and Cellular Glycobiology Unit, Department of Biological Sciences, Sungkyunkwan University) ;
  • Park, Young-Guk (Department of Orthodondritics, Kyung-Hee University College of Dental Medicine) ;
  • Kim, Cheorl-Ho (Molecular and Cellular Glycobiology Unit, Department of Biological Sciences, Sungkyunkwan University)
  • Received : 2006.06.07
  • Accepted : 2006.10.23
  • Published : 2007.04.30

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 $G{\ddot{o}}6976$, 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 $G{\ddot{o}}6976$ 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 $G{\ddot{o}}6976$ 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.

Keywords

Acknowledgement

Supported by : Ministry of Health & Welfare

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