The microtubule-associated protein, tau, is the principal component of paired helical filaments (PHFs) in Alzheimer's disease. PHF-tau is highly phosphorylated and a total of 25 sites of phosphorylation have so far been identified. Many of these sites are serine or threonine residues that are immediately followed in the sequence by proline residues, and hence are candidate phosphorylation sites for proline-directed kinases. In vitro, glycogen synthase kinase-3 (GSK-3), extracellular signal-related kinase-1 and -2, and mitogen-activated protein kinases, p38 kinase and c-jun N-terminal kinase, all phosphorylate many of these sites, although with different efficiencies for particular sites. Phosphorylation studies in transfected cells and neurons show that GSK-3 phosphorylates tau more extensively than do these other proline-directed kinases. Mutations in tau have been shown to affect in vitro phosphorylation of tau by GSK-3. The Arg406-->Trp (R406W) tau mutation also affects tau phosphorylation in cells.
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February 2001
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Conference Article|
February 01 2001
Sites of phosphorylation in tau and factors affecting their regulation
Brian H. Anderton;
Brian H. Anderton
1
*Department of Neuroscience, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, U.K.
1To whom correspondence should be addressed.
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Joanna Betts;
Joanna Betts
†Biomolecular Structure Unit, Glaxo-Wellcome Research and Development, Gunnels Wood Road, Stevenage SG1 2NY, U.K.
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Walter P. Blackstock;
Walter P. Blackstock
†Biomolecular Structure Unit, Glaxo-Wellcome Research and Development, Gunnels Wood Road, Stevenage SG1 2NY, U.K.
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Jean-Pierre Brion;
Jean-Pierre Brion
‡Laboratory of Pathology and Electron Microscopy, Université Libre de Bruxelles, 808 Route de Lennik, Bldg C-10, 1070 Brussels, Belgium
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Sara Chapman;
Sara Chapman
*Department of Neuroscience, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, U.K.
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James Connell;
James Connell
*Department of Neuroscience, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, U.K.
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Rejith Dayanandan;
Rejith Dayanandan
*Department of Neuroscience, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, U.K.
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Jean-Marc Gallo;
Jean-Marc Gallo
*Department of Neuroscience, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, U.K.
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Graham Gibb;
Graham Gibb
*Department of Neuroscience, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, U.K.
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Diane P. Hanger;
Diane P. Hanger
*Department of Neuroscience, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, U.K.
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Mike Hutton;
Mike Hutton
§The Birdsall Research Building, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, U.S.A.
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Efterpi Kardalinou;
Efterpi Kardalinou
*Department of Neuroscience, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, U.K.
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Karell Leroy;
Karell Leroy
‡Laboratory of Pathology and Electron Microscopy, Université Libre de Bruxelles, 808 Route de Lennik, Bldg C-10, 1070 Brussels, Belgium
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Simon Lovestone;
Simon Lovestone
*Department of Neuroscience, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, U.K.
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Till Mack;
Till Mack
*Department of Neuroscience, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, U.K.
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C.Hugh Reynolds;
C.Hugh Reynolds
*Department of Neuroscience, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, U.K.
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M. Van Slegtenhorst
M. Van Slegtenhorst
§The Birdsall Research Building, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, U.S.A.
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Publisher: Portland Press Ltd
Online ISSN: 1744-1439
Print ISSN: 0067-8694
© 2001 The Biochemical Society
2001
Biochem Soc Symp (2001) 67: 73–80.
Citation
Cora O'Neill, Brian Anderton, Brian H. Anderton, Joanna Betts, Walter P. Blackstock, Jean-Pierre Brion, Sara Chapman, James Connell, Rejith Dayanandan, Jean-Marc Gallo, Graham Gibb, Diane P. Hanger, Mike Hutton, Efterpi Kardalinou, Karell Leroy, Simon Lovestone, Till Mack, C.Hugh Reynolds, M. Van Slegtenhorst; Sites of phosphorylation in tau and factors affecting their regulation. Biochem Soc Symp 1 February 2001; 67 73–80. doi: https://doi.org/10.1042/bss0670073
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