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 p38aγ MAP kinase (SAPK3/p38γ) 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/p38γ-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.
Original language | English |
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Pages (from-to) | 1134-1145 |
Number of pages | 12 |
Journal | EMBO Journal |
Volume | 24 |
Issue number | 6 |
DOIs | |
Publication status | Published - 23 Mar 2005 |
Keywords
- Knockout
- Osmotic shock
- p38γ
- PDZ
- Stress-activated protein kinase-4/p38δ
ASJC Scopus subject areas
- General Neuroscience
- Molecular Biology
- General Biochemistry,Genetics and Molecular Biology
- General Immunology and Microbiology