| 1,25-Dihydroxyvitamin D3 activates Raf kinase and Raf perinuclear translocation via a protein kinase C-dependent pathway. | |
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MedLine Citation:
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PMID: 8227076 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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1,25-Dihydroxyvitamin D3's (D3) potential mitogenic mechanism of action was pursued in cultured rat hepatic Ito cells, a fibrogenic effector cell which proliferates in vivo during liver injury and fibrogenesis. D3 stimulated Ito cell DNA synthesis and potentiated platelet-derived growth factor-induced mitogenesis. D3's enhancement of [3H]thymidine incorporation was associated with nuclear Egr expression. Recent studies have causally linked the activated proto-oncogene c-Raf with downstream Egr induction. The serine-threonine kinase Raf protein is phosphorylation-activated by a large array of agonists including plasma membrane and cytoplasmic tyrosine kinases but has not previously been associated with the steroid superfamily of mediators. To consider potential prenuclear acute pathways of D3-induced stimulation, the activation of Raf was examined following D3 exposure. D3 induced Raf activation as assessed via (a) enhanced Raf phosphorylation following in vivo 32P labeling, (b) enhanced kinase function utilizing exogenous histone 1 protein as substrate, and (c) the shift in Raf physical localization changing from a diffuse cytoplasmic distribution to a perinuclear domain. A similar activation of Raf kinase was found in 3T3 cells exposed to D3 with enhanced histone phosphorylation detectable within 1 min following stimulation. The proximal cascade leading to Raf kinase activation may involve a protein kinase activity was severely attenuated by stimulated kinase activity was severely attenuated by previous phorbol ester treatment for 20 h or staurosporine pretreatment. |
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Authors:
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T W Lissoos; D W Beno; B H Davis |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 268 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 1993 Nov |
Date Detail:
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Created Date: 1993-12-20 Completed Date: 1993-12-20 Revised Date: 2009-11-19 |
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: 25132-8 Citation Subset: IM |
Affiliation:
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Department of Medicine, University of Chicago, Illinois 60637. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3T3 Cells Animals Biological Transport Calcitriol / pharmacology* Cells, Cultured Enzyme Activation Male Mice Platelet-Derived Growth Factor / pharmacology Protein Kinase C / metabolism* Protein-Serine-Threonine Kinases / metabolism* Proto-Oncogene Proteins / metabolism* Proto-Oncogene Proteins c-raf Rats Rats, Sprague-Dawley Receptor, Epidermal Growth Factor / metabolism Tetradecanoylphorbol Acetate / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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DK 07074-18/DK/NIDDK NIH HHS; DK 42086/DK/NIDDK NIH HHS; DK40223/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Platelet-Derived Growth Factor; 0/Proto-Oncogene Proteins; 16561-29-8/Tetradecanoylphorbol Acetate; 32222-06-3/Calcitriol; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-raf; EC 2.7.11.13/Protein Kinase C |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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