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| Content Provider | Journal of Biological Chemistry (JBC) |
|---|---|
| Author | Wang, Qiming J. Bhattacharyya, Dipak Garfield, Susan Nacro, Kassoum Marquez, Victor E. Blumberg, Peter M. |
| Abstract | Enzyme localization often plays a controlling role in determining its activity and specificity. Protein kinase C (PKC) has long been known to translocate in response to physiological stimuli as well as to exogenous ligands such as the phorbol esters. We report here that different phorbol derivatives and related ligands, selected for differences in chemical structure and profile of biological activity, induce distinct patterns of redistribution of PKC δ. Localization of a PKC δ-green fluorescent protein (GFP) fusion construct was monitored in living Chinese hamster ovary cells as a function of ligand, concentration, and time using confocal laser scanning microscopy. δ-PKC-GFP was expressed predominantly in the cytoplasm, with some in the nucleus and perinuclear region. Phorbol 12-myristate 13-acetate (PMA) induced plasma membrane translocation followed by slower nuclear membrane translocation. As the concentration of PMA increased, the proportion of nuclear to plasma membrane localization increased markedly. In contrast to PMA, bryostatin 1, a unique activator of PKC that induces a subset of PMA-mediated responses while antagonizing others, at all doses induced almost exclusively nuclear membrane translocation. Like PMA, the complete tumor promoter 12-deoxyphorbol 13-tetradecanoate induced plasma membrane and slower nuclear membrane translocation, whereas the inhibitor of tumor promotion 12-deoxyphorbol 13-phenylacetate, which differs only in its side chain, induced a distinctive distribution of PKC δ-GFP. Finally, the novel constrained diacylglycerol derivative B8-DL-B8 induced a slow Golgi localization. We speculate that differential control of PKC δ localization may provide an interesting strategy for producing ligands with differential biological consequences. |
| Related Links | http://www.jbc.org/content/274/52/37233.abstract |
| Ending Page | 37239 |
| Starting Page | 37233 |
| Page Count | 7 |
| File Format | HTM / HTML PDF |
| ISSN | 00219258 |
| Journal | Journal of Biological Chemistry (JBC) |
| Issue Number | 52 |
| Volume Number | 274 |
| DOI | 10.1074/jbc.274.52.37233 |
| e-ISSN | 1083351X |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 1999-12-24 |
| Access Restriction | Open |
| Subject Keyword | Diacylglycerol (DAG) Green fluorescent protein (GFP) Protein kinase C (PKC) Phorbol 12-myristate 13-acetate (PMA) Chinese hamster ovary (CHO) CELL BIOLOGY AND METABOLISM (dl)-(Z)-{1-(hydroxymethyl)-4-[4-methyl-3-(methylethyl)pentylidene]-3-oxo-2- oxolanyl}methyl-4-methyl-3-(methylethyl)pentanoate (B8-DL-B8) |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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