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

Guadalupe Sabio; James Simon Campbell Arthur; Yvonne Kuma; Mark Peggie; Julia Carr; Vicky Murray-Tait; Francisco Centeno; Michel Goedert; Nicholas A. Morrice; Ana Cuenda

doi:10.1038/sj.emboj.7600578

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

Guadalupe Sabio
, James Simon Campbell Arthur
, Yvonne Kuma
, Mark Peggie
, Julia Carr
, Vicky Murray-Tait
, Francisco Centeno
, Michel Goedert
, Nicholas A. Morrice
, Ana Cuenda (Lead / Corresponding author)

Research output: Contribution to journal › Article › peer-review

212 Citations (Scopus)

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
Pages (from-to)	1134-1145
Number of pages	12
Journal	EMBO Journal
Volume	24
Issue number	6
DOIs	https://doi.org/10.1038/sj.emboj.7600578
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

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10.1038/sj.emboj.7600578

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title = "p38γ 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 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.",

keywords = "Knockout, Osmotic shock, p38γ, PDZ, Stress-activated protein kinase-4/p38δ",

author = "Guadalupe Sabio and Arthur, \{James Simon Campbell\} and Yvonne Kuma and Mark Peggie and Julia Carr and Vicky Murray-Tait and Francisco Centeno and Michel Goedert and Morrice, \{Nicholas A.\} and Ana Cuenda",

year = "2005",

month = mar,

day = "23",

doi = "10.1038/sj.emboj.7600578",

language = "English",

volume = "24",

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journal = "EMBO Journal",

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T1 - p38γ regulates the localisation of SAP97 in the cytoskeleton by modulating its interaction with GKAP

AU - Sabio, Guadalupe

AU - Arthur, James Simon Campbell

AU - Kuma, Yvonne

AU - Peggie, Mark

AU - Carr, Julia

AU - Murray-Tait, Vicky

AU - Centeno, Francisco

AU - Goedert, Michel

AU - Morrice, Nicholas A.

AU - Cuenda, Ana

PY - 2005/3/23

Y1 - 2005/3/23

N2 - 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.

AB - 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.

KW - Knockout

KW - Osmotic shock

KW - p38γ

KW - PDZ

KW - Stress-activated protein kinase-4/p38δ

UR - https://www.scopus.com/pages/publications/20244365497

U2 - 10.1038/sj.emboj.7600578

DO - 10.1038/sj.emboj.7600578

M3 - Article

C2 - 15729360

AN - SCOPUS:20244365497

SN - 0261-4189

VL - 24

SP - 1134

EP - 1145

JO - EMBO Journal

JF - EMBO Journal

IS - 6

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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