Retinoids as ligands and coactivators of protein kinase C alpha Journal Article
| Authors: | Imam, A.; Hoyos, B.; Swenson, C.; Levi, E.; Chua, R.; Viriya, E.; Hammerling, U. |
| Article Title: | Retinoids as ligands and coactivators of protein kinase C alpha |
| Abstract: | Whereas retinoic acids control nuclear events, a second class of retinol metabolites, that is, the hydroxylated forms exemplified by 14-hydroxy-retro-retinol (HRR), operate primarily in the cytoplasm. They function as regulatory cofactors for cell survival/cell death decisions. In accordance with these biological aspects, we demonstrate that these retinoids bound protein kinase C (PKC) alpha with nanomolar affinity and markedly enhance the activation of PKC alpha and the entire downstream MAP kinase pathway by reactive oxygen species. HRR was 10 times more efficient than retinol, and the optimum doses are 10-7 and 10-6 M, respectively. PKC alpha activation was reversed rapidly by imposition of reducing conditions. The retinoid binding site was mapped to the first cysteine-rich region in the regulatory domain, C1A, yet was distinct from the binding sites of diacylglycerol and phorbol esters. The C1B domain bound retinoids poorly. The emerging theme is that retinoids serve as redox regulators of protein kinase C. |
| Keywords: | signal transduction; dose response; mouse; animal; metabolism; animals; mice; biological model; models, biological; map kinase signaling system; protein binding; enzyme activation; drug effect; dose-response relationship, drug; chemistry; ligand; drug derivative; reactive oxygen species; reactive oxygen metabolite; ligands; binding site; protein structure, tertiary; protein kinase c; binding sites; hydrogen peroxide; retinol; protein tertiary structure; cell strain 3t3; oxidation reduction reaction; oxidation-reduction; retinoid; cysteine; isoenzymes; 3t3 cells; protein kinase c alpha; protein kinase c-alpha; vitamin a; retinoids; isoenzyme; article; 14 hydroxy 4,14 retro retinol; 14-hydroxy-4,14-retro-retinol; prkca protein, mouse |
| Journal Title: | FASEB Journal |
| Volume: | 15 |
| Issue: | 1 |
| ISSN: | 0892-6638 |
| Publisher: | Federation of American Societies for Experimental Biology |
| Date Published: | 2001-01-01 |
| Start Page: | 28 |
| End Page: | 30 |
| Language: | English |
| PUBMED: | 11099483 |
| PROVIDER: | scopus |
| DOI: | 10.1096/fj.00-0329fje |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
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