Bacterial lipopolysaccharide has structural similarity to ceramide and stimulates ceramide-activated protein kinase in myeloid cells Journal Article
| Authors: | Joseph, C. K.; Wright, S. D.; Bornmann, W. G.; Randolph, J. T.; Kumar, E. R.; Bittman, R.; Liu, J.; Kolesnick, R. N. |
| Article Title: | Bacterial lipopolysaccharide has structural similarity to ceramide and stimulates ceramide-activated protein kinase in myeloid cells |
| Abstract: | Bacterial lipopolysaccharide (LPS), tumor necrosis factor (TNF)-α and interleukin-1β (IL-1β) stimulate similar cellular responses. TNF-α and IL- 1β are known to initiate signaling through a pathway involving hydrolysis of sphingomyelin to ceramide (Kolesnick, R. N., and Golde, D. W. (1994) Cell 77, 325-328). In this system, ceramide acts as a second messenger stimulating a ceramide-activated serine/threonine protein kinase. The present studies demonstrate that LPS, like TNF and IL-1, stimulates ceramide-activated protein kinase activity in human leukemia (HL-60) cells and in freshly isolated human neutrophils. Lipid A, the biologically active core of LPS, enhanced kinase activity in a time- and concentration-dependent manner. As little as 10 nM lipid A was effective, and a maximal effect occurred with 500 nM lipid A, increasing kinase activity 5-fold. Native LPS similarly induced kinase activation. This effect of LPS was markedly enhanced by LPS binding protein and required the LPS receptor CD14. In contrast to TNF and IL-1, LPS did not cause sphingomyelin hydrolysis and thus stimulates ceramide-activated protein kinase without generating ceramide. Molecular modeling showed strong structural similarity between ceramide and a region of lipid A. Based on these observations, we propose that LPS stimulates cells by mimicking the second messenger function of ceramide. |
| Keywords: | human cell; cells, cultured; enzyme activation; enzyme activity; amino acid sequence; molecular sequence data; tumor necrosis factor-alpha; enzyme analysis; protein-serine-threonine kinases; models, molecular; binding sites; bone marrow cell; protein kinase; molecular model; ceramide; ceramides; interleukin-1; carbohydrate conformation; lipopolysaccharides; cell strain hl 60; second messenger systems; bacterium lipopolysaccharide; lipid a; humans; human; priority journal; article |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 269 |
| Issue: | 26 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 1994-07-01 |
| Start Page: | 17606 |
| End Page: | 17610 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 8021269 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- Source: Scopus |
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