Activation of c-Raf kinase by ultraviolet light: Regulation by retinoids Journal Article
| Authors: | Hoyos, B.; Imam, A.; Korichneva, I.; Levi, E.; Chua, R.; Hammerling, U. |
| Article Title: | Activation of c-Raf kinase by ultraviolet light: Regulation by retinoids |
| Abstract: | The present study highlights retinoids as modulators of c-Raf kinase activation by UV light. Whereas a number of retinoids, including retinol, 14-hydroxyretroretinol, anhydroretinol (AR), and retinoic acid bound the c-Raf cysteine-rich domain (CRD) with equal affinity in vitro as well as in vivo, they displayed different, even opposing, effects on UV-mediated kinase activation; retinol and 14-hydroxyretroretinol augmented responses, whereas retinoic acid and AR were inhibitory. Oxidation of thiol groups of cysteines by reactive oxygen, generated during UV irradiation, was the primary event in c-Raf activation, causing the release of zinc ions and, by inference, a change in CRD structure. Retinoids modulated these oxidation events directly: retinol enhanced, whereas AR suppressed, zinc release, precisely mirroring the retinoid effects on c-Raf kinase activation. Oxidation of c-Raf was not sufficient for kinase activation, productive interaction with Ras being mandatory. Further, canonical tyrosine phosphorylation and the action of phosphatase were essential for optimal c-Raf kinase competence. Thus, retinoids bound c-Raf with high affinity, priming the molecule for UV/reactive oxygen species-mediated changes of the CRD that set off GTP-Ras interaction and, in context with an appropriate phosphorylation pattern, lead to full phosphotransferase capacity. |
| Keywords: | controlled study; protein phosphorylation; unclassified drug; nonhuman; binding affinity; protein domain; ultraviolet radiation; animal cell; phosphatase; protein binding; protein interaction; enzyme activation; phosphorylation; animalia; irradiation; reactive oxygen species; reactive oxygen metabolite; ras proteins; retinol; zinc; ultraviolet rays; biochemistry; phosphotransferase; enzymes; oxidation-reduction; retinoid; proto-oncogene proteins c-raf; retinoids; thiol derivative; anhydroretinol; c raf kinase; cysteine derivative; retinol derivative; priority journal; article; 14 hydroxyretroretinol; guanosine triphosphate derivative; oxidation kinetics |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 277 |
| Issue: | 26 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2002-06-28 |
| Start Page: | 23949 |
| End Page: | 23957 |
| Language: | English |
| DOI: | 10.1074/jbc.M110750200 |
| PUBMED: | 11971897 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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10Koritchneva -
3
Imam -
23Hoyos -
21
Chua -
79Hammerling -
17
Levi
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