Kinase suppressor of Ras is ceramide-activated protein kinase Journal Article
| Authors: | Zhang, Y.; Yao, B.; Delikat, S.; Bayoumy, S.; Lin, X. H.; Basu, S.; McGinley, M.; Chan-Hui, P. Y.; Lichenstein, H.; Kolesnick, R. |
| Article Title: | Kinase suppressor of Ras is ceramide-activated protein kinase |
| Abstract: | A proline-directed serine/threonine ceramide-activated protein (CAP) kinase mediates transmembrane signaling through the sphingomyelin pathway. CAP kinase reportedly initiates proinflammatory TNFα action by phosphorylating and activating Raf-1. The present studies delineate kinase suppressor of Ras (KSR), identified genetically in Caenorhabditis elegans and Drosophila, as CAP kinase. Mouse KSR, like CAP kinase, renatures and autophosphorylates as a 100-kDa membrane-bound polypeptide. KSR overexpression constitutively activates Raf-1. TNFα or ceremide analogs markedly enhance KSR autophosphorylation and its ability to complex with, phosphorylate, and activate Raf-1. In vitro, low nanomolar concentrations of natural ceramide stimulate KSR to autophosphorylate, and transactivate Raf- 1. Other lipid second messengers were ineffective. Moreover, Thr269, the Raf-1 site phosphorylated by CAP kinase, is also recognized by KSR. Thus, by previously established criteria, KSR appears to be CAP kinase. |
| Keywords: | signal transduction; protein phosphorylation; raf protein; nonhuman; mouse; animals; mice; protein kinases; drosophila; protein serine threonine kinase; autophosphorylation; cos cells; phosphorylation; enzyme regulation; amino acid sequence; molecular sequence data; tumor necrosis factor alpha; tumor necrosis factor-alpha; protein-serine-threonine kinases; threonine; ras protein; caenorhabditis elegans; ras proteins; mutagenesis; ceramide; ceramides; gene expression regulation, enzymologic; second messenger; humans; priority journal; article |
| Journal Title: | Cell |
| Volume: | 89 |
| Issue: | 1 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 1997-04-04 |
| Start Page: | 63 |
| End Page: | 72 |
| Language: | English |
| PUBMED: | 9094715 |
| PROVIDER: | scopus |
| DOI: | 10.1016/S0092-8674(00)80183-X |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
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