| Regulation of receptor-mediated protein kinase C membrane trafficking by autophosphorylation. | |
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MedLine Citation:
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PMID: 10828076 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Signal transduction via protein kinase C (PKC) is closely regulated by its subcellular localization. In response to activation of cell-surface receptors, PKC is directed to the plasma membrane by two membrane-targeting domains, namely the C1 and C2 regions. This is followed by the return of the enzyme to the cytoplasm, a process shown recently to require PKC autophosphorylation (Feng, X., and Hannun, Y. A. (1998) J. Biol. Chem. 273, 26870-26874). In the present study, we examined mechanisms of translocation and reverse translocation and the role of autophosphorylation in these processes. By visualizing the trafficking of wild-type as well as mutant PKCbetaII in live cells, we demonstrated that in response to cell-surface receptor activation, the function of the C1 region is required but not sufficient for recruitment of the enzyme to the plasma membrane. The C2 region is also critical in anchoring the enzyme to the plasma membrane. Furthermore, the inability of a kinase-deficient PKC to undergo reverse translocation was restored by the addition of intracellular calcium chelators, suggesting a role for the C2 region in the persistent phase of translocation. On the other hand, the inability of a C2 deletion mutant (C1 region intact) to translocate in response to agonist was reversed in mutants lacking kinase activity or by mutation of the Ser(660) autophosphorylation site to alanine, suggesting that autophosphorylation of this site is required for opposing the action of the C2 region. Therefore, the membrane-targeting function of the C1 region is facilitated by the C2 region and appears to be opposed by autophosphorylation. Taken together, these findings provide novel evidence of the functional regulation of reversible PKC membrane localization by autophosphorylation, and they show that the dynamic translocation of PKC in response to agonists is tightly regulated in a collaborative fashion by the C1 and C2 regions in balance with the effects of autophosphorylation. |
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Authors:
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X Feng; K P Becker; S D Stribling; K G Peters; Y A Hannun |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 275 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2000 Jun |
Date Detail:
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Created Date: 2000-07-11 Completed Date: 2000-07-11 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 17024-34 Citation Subset: IM |
Affiliation:
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Departments of Cell Biology and Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Biological Transport Cell Line Cell Membrane / enzymology Green Fluorescent Proteins Humans Luminescent Proteins / metabolism Phosphorylation Protein Kinase C / metabolism* Receptors, Cell Surface / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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HL-43707/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Luminescent Proteins; 0/Receptors, Cell Surface; 147336-22-9/Green Fluorescent Proteins; EC 2.7.11.13/Protein Kinase C |
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