title: p38gamma regulates the localisation of SAP97 in the cytoskeleton by modulating its interaction with GKAP.
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.
authors.affiliation: MRC Protein Phosphorylation Unit, University of Dundee, Dundee, UK.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Sabio
authors.forename: James Simon Campbell
authors.initials: JS
authors.lastname: Arthur
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Kuma
authors.forename: Mark
authors.initials: M
authors.lastname: Peggie
authors.forename: Julia
authors.initials: J
authors.lastname: Carr
authors.forename: Vicky
authors.initials: V
authors.lastname: Murray-Tait
authors.forename: Francisco
authors.initials: F
authors.lastname: Centeno
authors.forename: Michel
authors.initials: M
authors.lastname: Goedert
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Morrice
authors.forename: Ana
authors.initials: A
authors.lastname: Cuenda
mesh_terms: 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
chemical_list: 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
references.citation: Int J Dev Biol. 2002;46(4):511-8
references.pmid: 12141438
references.citation: Biophys J. 2003 Jul;85(1):223-35
references.pmid: 12829478
references.citation: EMBO J. 2000 Nov 1;19(21):5740-51
references.pmid: 11060025
references.citation: J Biol Chem. 1997 May 2;272(18):11943-51
references.pmid: 9115257
references.citation: Bioessays. 2003 Jun;25(6):542-53
references.pmid: 12766944
references.citation: J Cell Biol. 1997 Feb 10;136(3):669-78
references.pmid: 9024696
references.citation: J Biol Chem. 1998 Jan 16;273(3):1832-7
references.pmid: 9430735
references.citation: Genomics. 1997 May 1;41(3):501-2
references.pmid: 9169156
references.citation: Neuron. 1999 Jul;23(3):569-82
references.pmid: 10433268
references.citation: J Neurosci. 2004 Jan 14;24(2):378-88
references.pmid: 14724236
references.citation: Biochem J. 2004 May 15;380(Pt 1):19-30
references.pmid: 14741046
references.citation: Biochem Soc Symp. 1999;64:79-89
references.pmid: 10207622
references.citation: Am J Physiol Cell Physiol. 2002 Sep;283(3):C850-65
references.pmid: 12176742
references.citation: Biochem J. 2000 Oct 1;351(Pt 1):95-105
references.pmid: 10998351
references.citation: Am J Physiol. 1999 May;276(5 Pt 1):C995-C1011
references.pmid: 10329946
references.citation: Mol Cell Biol. 2002 Apr;22(8):2871-81
references.pmid: 11909979
references.citation: Physiol Rev. 2001 Apr;81(2):807-69
references.pmid: 11274345
references.citation: Proc Natl Acad Sci U S A. 2000 May 9;97(10):5167-72
references.pmid: 10779557
references.citation: FEBS Lett. 2001 Jul 27;502(1-2):21-4
references.pmid: 11478941
references.citation: EMBO J. 1997 Jun 16;16(12):3563-71
references.pmid: 9218798
references.citation: Cell. 1999 Aug 6;98(3):353-63
references.pmid: 10458610
references.citation: Trends Cell Biol. 2000 Jul;10(7):274-80
references.pmid: 10856930
references.citation: Mol Cell Biol. 2003 Jan;23(1):370-81
references.pmid: 12482988
references.citation: Nat Rev Mol Cell Biol. 2004 Aug;5(8):601-13
references.pmid: 15366704
references.citation: J Neurosci. 1999 Aug 1;19(15):6506-18
references.pmid: 10414979
references.citation: J Cell Sci. 1998 Apr;111 ( Pt 8):1071-80
references.pmid: 9512503
references.citation: J Invest Dermatol. 2001 Nov;117(5):1290-5
references.pmid: 11710946
references.citation: J Cell Sci. 2001 Mar;114(Pt 5):987-98
references.pmid: 11181181
references.citation: J Biol Chem. 1999 Apr 30;274(18):12626-31
references.pmid: 10212242
references.citation: Mol Cell Biol. 2002 Mar;22(6):1778-91
references.pmid: 11865057
references.citation: J Neurosci. 1995 Mar;15(3 Pt 2):2354-66
references.pmid: 7891172
references.citation: J Biol Chem. 2003 Nov 7;278(45):44745-52
references.pmid: 12933808
references.citation: Genes Cells. 2000 Mar;5(3):203-10
references.pmid: 10759891
references.citation: Am J Physiol Renal Physiol. 2003 Aug;285(2):F336-47
references.pmid: 12724128
references.citation: J Biol Chem. 2004 Mar 12;279(11):10157-66
references.pmid: 14699157
references.citation: Biochem J. 2004 Apr 1;379(Pt 1):133-9
references.pmid: 14680475
references.citation: Mol Cell Biol. 1998 Oct;18(10):5838-51
references.pmid: 9742101
references.citation: J Biol Chem. 1997 Nov 21;272(47):29934-41
references.pmid: 9368070
references.citation: J Biomol Tech. 2002 Sep;13(3):119-30
references.pmid: 19498976
references.citation: DNA Seq. 1999;10(4-5):229-43
references.pmid: 10727080