Glycobiology Advance Access published online on September 22, 2004
Glycobiology, doi:10.1093/glycob/cwh156
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1 National Research Laboratory for Glycobiology, MOST, Korea; Department of Biochemistry and Molecular Biology, College of Oriental Medicine, Dongguk University, Kyungju 780-714, South Korea
* To whom correspondence should be addressed. E-mail: chkimbio{at}dongguk.ac.kr.
Previous studies have demonstrated that the activity of GM3 synthase and GM3 content are increased during the differentiation of human promyelocytic leukemia HL-60 cells into the monocyte/macrophage lineage after phorbol 12-myristate13-acetate (PMA) treatment. However, the molecular mechanisms involved in transcriptional activation of GM3 synthase during differentiation of PMA-induced HL-60 cells are not well understood. As evidenced by Western blot analysis, PMA induced the marked activation of protein kinase C (PKC)/extracellular regulated kinases (ERKs) signal transduction pathway during the differentiation of HL-60 cells. In addition, PKC/ERKs activation induced by PMA, in HL-60 cells, led to the phosphorylation of cAMP-responsive element binding protein (CREB) as a transcription factor. In PMA-stimulated HL-60 cells, the PKC/ERKs-dependent CREB activation regulated expression of GM3 synthase, inducing a synthesis of ganglioside GM3 product. On the other hand, although ganglioside GM3 was shown to be able to induce the differentiation of HL-60 cells into the monocyte/macrophage lineage, effect of ganglioside GM3 on expression of CD11b as a differentiation marker in HL-60 cells has been not reported yet. Interstingly, the increased ganglioside GM3 through PKC/ERKs/CREB-dependent pathway by PMA resulted in an increase of CD11b surface antigen expression and induction of HL-60 cells adherence. Whereas, treatment of L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), glucosylceramide synthase inhibitor decreased in an induction of not only CD11b expression but also cellular adherence by reduction of PMA-induced ganglioside GM3. Furthermore, treatment of HL-60 cells with an exogenous ganglioside GM3 induce CD11b expression. These results first show that the enhanced expression of GM3 synthase through PKC/ERKs-dependent CREB activation by PMA is associated with the differentiation of HL-60
cells by inducing expression of CD 11b known as a monocyte/macrophage differentiation maker.
Revised September 18, 2004
Accepted September 21, 2004
ORIGINAL ARTICLES
Molecular mechanism for transcriptional activation of ganglioside GM3 synthase and its function in differentiation of HL-60 cells
2 Faculty of Biotechnolgy, Dong-A University, Pusan 604-714, South Korea
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