BAD enables ceramide to signal apoptosis via Ras and Raf-1 Journal Article
| Authors: | Basu, S.; Bayoumy, S.; Zhang, Y.; Lozano, J.; Kolesnick, R. |
| Article Title: | BAD enables ceramide to signal apoptosis via Ras and Raf-1 |
| Abstract: | Prior investigations document that proliferative signaling cascades, under some circumstances, initiate apoptosis, although mechanisms that dictate the final outcome are largely unknown. In COS-7 cells, ceramide signals Raf-1 activation through Ras (Zhang, Y., Yao, B, Delikat, S., Bayoumy, S., Lin, X. H., Basu, S., McGinley, M., ChanHui, P. Y., Lichenstein, H., and Kolesnick, R. (1997) Cell 89, 63-72), but not apoptosis. However, expression of small amounts of the pro-apoptotic Bcl-2 family member, BAD, conferred ceramide-induced apoptosis onto COS-7 cells. Ceramide signaled apoptosis in BAD-expressing cells by a pathway involving sequentially kinase suppressor of Ras (KSR)/ceramide-activated protein kinase, Ras, c-Raf-1, and MEK1. Downstream, this pathway linked to BAD dephosphorylation at serine 136 by prolonged inactivation of Akt/PKB. Further, mutation of BAD at serine 136 abrogated ceramide signaling of apoptosis. The present study indicates that when ceramide signals through the Ras/Raf cascade, the availability of a single target, BAD, may dictate an apoptotic outcome. |
| Keywords: | signal transduction; mitogen activated protein kinase; controlled study; protein phosphorylation; unclassified drug; proto-oncogene proteins; raf protein; nonhuman; animal cell; animals; protein bcl 2; apoptosis; serine; genetic transcription; cos cells; phosphorylation; protein-serine-threonine kinases; carrier proteins; proto-oncogene proteins c-akt; ras protein; ras proteins; protein kinase; ceramide; ceramides; proto-oncogene proteins c-raf; enzyme repression; protein bad; bcl-associated death protein; priority journal; article |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 273 |
| Issue: | 46 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 1998-11-13 |
| Start Page: | 30419 |
| End Page: | 30426 |
| Language: | English |
| DOI: | 10.1074/jbc.273.46.30419 |
| PUBMED: | 9804808 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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