p38γ regulates the localisation of SAP97 in the cytoskeleton by modulating its interaction with GKAP

• DOI: 10.1038/sj.emboj.7600578
• Publication Date: 2005-02-24T10:02:26Z
• Authors: Guadalupe Sabio; James Simon Campb...; Yvonne Kuma; Mark Peggie; Julia Carr; Vicky Murray-Tait; Francisco Centeno; Michel Goedert; Nicholas A Morrice; Ana Cuenda
• Keywords: 0301 basic medicine; 570; p38γ; /dk/atira/pure/subjectarea/asjc/1300/1312; Knockout; Nerve Tissue Proteins; Substrate Specificity; Discs Large Homolog 1 Protein; name=General Immunology and Microbiology; Mice; 03 medical and health sciences; Mitogen-Activated Protein Kinase 12; Osmotic Pressure; /dk/atira/pure/subjectarea/asjc/2800/2800; Cell Line, Tumor; name=General Biochemistry,Genetics and Molecular Biology; /dk/atira/pure/subjectarea/asjc/2400/2400; Animals; Drosophila Proteins; Humans; PDZ; Phosphorylation; Cell Shape; Cytoskeleton; Adaptor Proteins, Signal Transducing; Cell Size; Mice, Knockout; /dk/atira/pure/subjectarea/asjc/1300/1300; Membrane Proteins; name=Molecular Biology; name=General Neuroscience; SAP90-PSD95 Associated Proteins; Intercellular Junctions; Osmotic shock; Guanylate Kinases; Stress-activated protein kinase-4/p38δ

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.