Tumor necrosis factor-α activates the sphingomyelin signal transduction pathway in a cell-free system Journal Article
| Authors: | Dressler, K. A.; Mathias, S.; Kolesnick, R. N. |
| Article Title: | Tumor necrosis factor-α activates the sphingomyelin signal transduction pathway in a cell-free system |
| Abstract: | The mechanism of tumor necrosis factor (TNF)-α signaling is unknown. TNF-α signaling may involve sphingomyelin hydrolysis to ceramide by a sphingomyelinase and stimulation of a ceramide-activated protein kinase. In a cell-free system, TN-α induced a rapid reduction in membrane sphingomyelin content and a quantitative elevation in ceramide concentrations. Ceramide-activated protein kinase activity also increased. Kinase activation was mimicked by addition of sphingomyelinase but not by phospholipases A 2, C, or D. Reconstitution of this cascade in a cell-free system demonstrates tight coupling to the receptor, suggesting this is a signal transduction pathway for TNF-α. |
| Keywords: | signal transduction; human cell; protein kinases; receptor, epidermal growth factor; enzyme activation; tumor cells, cultured; phosphorylation; tumor necrosis factor alpha; protein kinase; in vitro; tumor necrosis factor; ceramides; receptors, cell surface; sphingomyelin phosphodiesterase; receptors, tumor necrosis factor; sphingomyelin; cell-free system; second messenger systems; sphingomyelins; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s. |
| Journal Title: | Science |
| Volume: | 255 |
| Issue: | 5052 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 1992-03-27 |
| Start Page: | 1715 |
| End Page: | 1718 |
| Language: | English |
| DOI: | 10.1126/science.1313189 |
| PUBMED: | 1313189 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Source: Scopus |
