biostudies-literatureUnknown24(6)Sabio GActivation 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 The EMBO journal1134-45https://www.ebi.ac.uk/biostudies/studies/S-EPMC556394biostudies-literaturep38gamma regulates the localisation of SAP97 in the cytoskeleton by modulating its interaction with GKAP.PMC556394Sabio GArthur JSGoedert MMurray-Tait VCenteno FMorrice NACuenda AKuma YCarr JPeggie Mfalsep38gamma 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 2005-01-01T00:00:00Z2005 Mar2026-07-15T11:13:56.277Z2019-03-27T01:08:42ZS-EPMC5563941572936010.1038/sj.emboj.7600578