Abstract
Activation of the p38 MAP kinase pathways is crucial for the adaptation of mammalian cells to changes in the osmolarity of the environment. Here we identify SAP97/hDlg, the mammalian homologue of the Drosophila tumour suppressor Dlg, as a physiological substrate for the p38gamma MAP kinase (SAPK3/p38gamma) isoform. SAP97/hDlg is a scaffold protein that forms multiprotein complexes with a variety of proteins and is targeted to the cytoskeleton by its association with the protein guanylate kinase-associated protein (GKAP). The SAPK3/p38gamma-catalysed phosphorylation of SAP97/hDlg triggers its dissociation from GKAP and therefore releases it from the cytoskeleton. This is likely to regulate the integrity of intercellular-junctional complexes, and cell shape and volume in response to osmotic stress.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Cell Line, Tumor
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Cell Shape / physiology
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Cell Size
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Cytoskeleton / chemistry
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Cytoskeleton / metabolism*
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Discs Large Homolog 1 Protein
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Drosophila Proteins
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Guanylate Kinases
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Humans
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Intercellular Junctions / metabolism
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Membrane Proteins
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Mice
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Mice, Knockout
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Mitogen-Activated Protein Kinase 12 / genetics
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Mitogen-Activated Protein Kinase 12 / physiology*
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Nerve Tissue Proteins / analysis
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Nerve Tissue Proteins / metabolism*
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Osmotic Pressure
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Phosphorylation
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SAP90-PSD95 Associated Proteins
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Substrate Specificity
Substances
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Adaptor Proteins, Signal Transducing
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DLG1 protein, human
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DLGAP1 protein, human
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Discs Large Homolog 1 Protein
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Dlg1 protein, mouse
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Dlgap1 protein, mouse
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Drosophila Proteins
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Mars protein, Drosophila
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Membrane Proteins
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Nerve Tissue Proteins
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SAP90-PSD95 Associated Proteins
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Mitogen-Activated Protein Kinase 12
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Guanylate Kinases