The native structure of the activated Raf protein kinase is a membrane-bound multi-subunit complex
Document Type
Journal ArticlePublication Date
1994-03-04Keywords
Amino Acid SequenceAnimals
Blotting, Western
CHO Cells
Calcium-Calmodulin-Dependent Protein Kinases
Cell Membrane
Chromatography, Gel
Cricetinae
Cytosol
Enzyme Activation
Immune Sera
Kinetics
Macromolecular Substances
Molecular Sequence Data
Molecular Weight
Peptides
Protein-Serine-Threonine Kinases
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-raf
Recombinant Fusion Proteins
Transfection
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Raf is a mitogen-stimulated protein kinase that functions as a component of the signaling cascade that leads to the stimulation of mitogen-activated protein kinase. Here we show that the native structure of Raf is a large multi-subunit protein complex with an apparent mass of 300-500 kDa that interacts with Ras and the mitogen-activated protein kinase kinase Mek. Analysis of the structure of the Raf complex demonstrates that it contains a single Raf protein kinase together with the molecular chaperones hsp90 and p50. The Raf-hsp90-p50 complex was observed in starved cells and in cells activated with serum or phorbol ester. Thus, changes in complex formation with hsp90 and p50 are not required for activation of the Raf protein kinase. However, Raf activation caused by Ras was associated with the translocation of the cytoplasmic Raf-hsp90-p50 complex to the cell membrane. Significantly, it is only the membrane-bound complex that exhibits increased protein kinase activity. Thus, the Ras-activated Raf protein kinase functions as a membrane-bound multi-subunit complex.Source
J Biol Chem. 1994 Mar 4;269(9):6695-701.Permanent Link to this Item
http://hdl.handle.net/20.500.14038/42479PubMed ID
8120027Related Resources
Link to Article in PubMedCollections
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