p38gamma regulates the localisation of SAP97 in the cytoskeleton by modulating its interaction with GKAP.
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.
Sabio
Guadalupe
G
MRC Protein Phosphorylation Unit, University of Dundee, Dundee, UK.
Arthur
James Simon Campbell
JS
Kuma
Yvonne
Y
Peggie
Mark
M
Carr
Julia
J
Murray-Tait
Vicky
V
Centeno
Francisco
F
Goedert
Michel
M
Morrice
Nicholas A
NA
Cuenda
Ana
A
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000502:physiology; D048429:Cell Size; D003599:Cytoskeleton / Q000737:chemistry / Q000378:metabolism*; D000074288:Discs Large Homolog 1 Protein; D029721:Drosophila Proteins; D051528:Guanylate Kinases; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D048291:Mitogen-Activated Protein Kinase 12 / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism*; D009997:Osmotic Pressure; D010766:Phosphorylation; D000074407:SAP90-PSD95 Associated Proteins; D013379:Substrate Specificity
D048868:Adaptor Proteins, Signal Transducing; C513314:DLG1 protein, human; C000614187:DLGAP1 protein, human; D000074288:Discs Large Homolog 1 Protein; C000614189:Dlg1 protein, mouse; C000614190:Dlgap1 protein, mouse; D029721:Drosophila Proteins; C000614192:Mars protein, Drosophila; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000074407:SAP90-PSD95 Associated Proteins; D048291:Mitogen-Activated Protein Kinase 12; D051528:Guanylate Kinases
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