| Protein kinase A blocks Raf-1 activity by stimulating 14-3-3 binding and blocking Raf-1 interaction with Ras. | |
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MedLine Citation:
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PMID: 12801936 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cyclic AMP (cAMP) blocks Raf-1 activation by stimulating its phosphorylation on serine 43 (Ser43), serine 233 (Ser233), and serine 259 (Ser259). We show here that phosphorylation of all three sites blocks Raf-1 binding to Ras.GTP in vivo and that cAMP stimulates binding of 14-3-3 proteins to Ser233 and Ser259. We also show that Raf-1 and protein kinase A (PKA) form a complex in vivo that is disrupted by cAMP and that ablation of PKA by use of small interfering RNA blocks phosphorylation by cAMP. The ability of PKA to block Raf-1 activation is ablated by the PKA inhibitor H89. These studies suggest that Raf-1 and cAMP form a signaling complex in cells. Upon activation of PKA, Raf-1 is phosphorylated and 14-3-3 binds, blocking Raf-1 recruitment to the plasma membrane and preventing its activation. |
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Authors:
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Nicolas Dumaz; Richard Marais |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2003-06-11 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 278 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2003 Aug |
Date Detail:
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Created Date: 2003-08-04 Completed Date: 2003-09-24 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: 29819-23 Citation Subset: IM |
Affiliation:
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Cancer Research UK Centre for Cell and Molecular Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, United Kingdom. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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14-3-3 Proteins 3T3 Cells Animals Binding Sites COS Cells Cell Culture Techniques Cell Membrane / metabolism Cyclic AMP / metabolism Cyclic AMP-Dependent Protein Kinases / physiology* Enzyme Activation Enzyme Inhibitors / pharmacology Isoquinolines / pharmacology Mice Peptides / chemistry Phosphorylation Precipitin Tests Protein Binding Proto-Oncogene Proteins c-raf / antagonists & inhibitors* RNA Interference Serine / chemistry Signal Transduction Sulfonamides* Time Factors Tyrosine 3-Monooxygenase / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/14-3-3 Proteins; 0/Enzyme Inhibitors; 0/Isoquinolines; 0/Peptides; 0/Sulfonamides; 127243-85-0/H 89; 56-45-1/Serine; 60-92-4/Cyclic AMP; EC 1.14.16.2/Tyrosine 3-Monooxygenase; EC 2.7.11.1/Proto-Oncogene Proteins c-raf; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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