p38γ通过调节SAP97与GKAP的相互作用来调控其在细胞骨架中的定位。
p38gamma regulates the localisation of SAP97 in the cytoskeleton by modulating its interaction with GKAP.
作者信息
Sabio Guadalupe, Arthur James Simon Campbell, Kuma Yvonne, Peggie Mark, Carr Julia, Murray-Tait Vicky, Centeno Francisco, Goedert Michel, Morrice Nicholas A, Cuenda Ana
机构信息
MRC Protein Phosphorylation Unit, University of Dundee, Dundee, UK.
出版信息
EMBO J. 2005 Mar 23;24(6):1134-45. doi: 10.1038/sj.emboj.7600578. Epub 2005 Feb 24.
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.
摘要
p38丝裂原活化蛋白激酶（MAP激酶）信号通路的激活对于哺乳动物细胞适应环境渗透压的变化至关重要。在此，我们鉴定出果蝇肿瘤抑制因子Dlg的哺乳动物同源物SAP97/hDlg，它是p38γ丝裂原活化蛋白激酶（应激激活蛋白激酶3/p38γ）亚型的生理底物。SAP97/hDlg是一种支架蛋白，可与多种蛋白质形成多蛋白复合物，并通过与鸟苷酸激酶相关蛋白（GKAP）结合而靶向细胞骨架。应激激活蛋白激酶3/p38γ催化的SAP97/hDlg磷酸化会触发其与GKAP解离，从而使其从细胞骨架上释放出来。这可能会调节细胞间连接复合物的完整性以及细胞形状和体积，以应对渗透压应激。
相似文献
1
p38gamma regulates the localisation of SAP97 in the cytoskeleton by modulating its interaction with GKAP.p38γ通过调节SAP97与GKAP的相互作用来调控其在细胞骨架中的定位。
EMBO J. 2005 Mar 23;24(6):1134-45. doi: 10.1038/sj.emboj.7600578. Epub 2005 Feb 24.
2
p38gamma regulates interaction of nuclear PSF and RNA with the tumour-suppressor hDlg in response to osmotic shock.p38γ 通过调节核 PSF 与肿瘤抑制因子 hDlg 及其 RNA 的相互作用响应渗透冲击。
J Cell Sci. 2010 Aug 1;123(Pt 15):2596-604. doi: 10.1242/jcs.066514. Epub 2010 Jul 6.
3
Stress- and mitogen-induced phosphorylation of the synapse-associated protein SAP90/PSD-95 by activation of SAPK3/p38gamma and ERK1/ERK2.应激和有丝分裂原通过激活SAPK3/p38γ和ERK1/ERK2诱导突触相关蛋白SAP90/PSD-95发生磷酸化。
Biochem J. 2004 May 15;380(Pt 1):19-30. doi: 10.1042/BJ20031628.
4
Intramolecular interactions regulate SAP97 binding to GKAP.分子内相互作用调节SAP97与GKAP的结合。
EMBO J. 2000 Nov 1;19(21):5740-51. doi: 10.1093/emboj/19.21.5740.
5
BIRB796 inhibits all p38 MAPK isoforms in vitro and in vivo.BIRB796在体外和体内均能抑制所有p38丝裂原活化蛋白激酶亚型。
J Biol Chem. 2005 May 20;280(20):19472-9. doi: 10.1074/jbc.M414221200. Epub 2005 Mar 8.
6
Proteolysis of the tumour suppressor hDlg in response to osmotic stress is mediated by caspases and independent of phosphorylation.肿瘤抑制因子hDlg在渗透压应激反应中的蛋白水解作用由半胱天冬酶介导，且与磷酸化无关。
FEBS J. 2009 Jan;276(2):387-400. doi: 10.1111/j.1742-4658.2008.06783.x. Epub 2008 Nov 28.
7
Association of cottontail rabbit papillomavirus E6 oncoproteins with the hDlg/SAP97 tumor suppressor.棉尾兔乳头瘤病毒E6癌蛋白与hDlg/SAP97肿瘤抑制因子的关联。
J Cell Biochem. 2005 Apr 1;94(5):1038-45. doi: 10.1002/jcb.20383.
8
Modulation of tau phosphorylation and intracellular localization by cellular stress.细胞应激对tau蛋白磷酸化及细胞内定位的调节作用
Biochem J. 2000 Jan 15;345 Pt 2(Pt 2):263-70.
9
Synaptic glutamate receptor clustering in mice lacking the SH3 and GK domains of SAP97.缺乏SAP97的SH3和GK结构域的小鼠中突触谷氨酸受体的聚集
Eur J Neurosci. 2002 Oct;16(8):1517-22. doi: 10.1046/j.1460-9568.2002.02228.x.
10
Identification of the mouse homologue of human discs large and rat SAP97 genes.人类盘状大蛋白和大鼠SAP97基因的小鼠同源物的鉴定。
Biochim Biophys Acta. 1997 Nov 28;1362(1):1-5. doi: 10.1016/s0925-4439(97)00059-8.
引用本文的文献
1
Cirrhotic Cardiomyopathy: Bridging Hepatic and Cardiac Pathophysiology in the Modern Era.肝硬化心肌病：现代肝脏与心脏病理生理学的桥梁
J Clin Med. 2025 Aug 25;14(17):5993. doi: 10.3390/jcm14175993.
2
Knocking out p38α+p38β+p38γ is required to abort the myogenic program in C2C12 myoblasts and to impose uncontrolled proliferation.敲除p38α + p38β + p38γ对于终止C2C12成肌细胞中的生肌程序并导致不受控制的增殖是必需的。
J Biol Chem. 2025 Mar;301(3):108281. doi: 10.1016/j.jbc.2025.108281. Epub 2025 Feb 6.
3
p38α Mitogen-Activated Protein Kinase-An Emerging Drug Target for the Treatment of Alzheimer's Disease.p38α 丝裂原活化蛋白激酶——阿尔茨海默病治疗的一个新兴药物靶点。
Molecules. 2024 Sep 13;29(18):4354. doi: 10.3390/molecules29184354.
4
p38γ/δ activation alters cardiac electrical activity and predisposes to ventricular arrhythmia.p38γ/δ 激活改变心脏电活动，易导致室性心律失常。
Nat Cardiovasc Res. 2023 Dec;2(12):1204-1220. doi: 10.1038/s44161-023-00368-x. Epub 2023 Nov 27.
5
MAPK13 controls structural remodeling and disease after epithelial injury.丝裂原活化蛋白激酶13（MAPK13）控制上皮损伤后的结构重塑和疾病。
bioRxiv. 2024 Aug 10:2024.05.31.596863. doi: 10.1101/2024.05.31.596863.
6
Phosphorylation of cell cycle and apoptosis regulatory protein-1 by stress activated protein kinase P38γ is a novel mechanism of apoptosis signaling by genotoxic chemotherapy.应激激活蛋白激酶P38γ对细胞周期及凋亡调节蛋白-1的磷酸化作用是基因毒性化疗引发凋亡信号的一种新机制。
Front Oncol. 2024 May 2;14:1376666. doi: 10.3389/fonc.2024.1376666. eCollection 2024.
7
G-quadruplex structural dynamics at MAPK12 promoter dictates transcriptional switch to determine stemness in breast cancer.丝裂原活化蛋白激酶12（MAPK12）启动子处的G-四链体结构动力学决定转录开关，以确定乳腺癌的干性。
Cell Mol Life Sci. 2024 Jan 12;81(1):33. doi: 10.1007/s00018-023-05046-6.
8
p38γ MAPK delays myelination and remyelination and is abundant in multiple sclerosis lesions.p38γ丝裂原活化蛋白激酶会延迟髓鞘形成和髓鞘再生，且在多发性硬化症病灶中含量丰富。
Brain. 2024 May 3;147(5):1871-1886. doi: 10.1093/brain/awad421.
9
p38γ and p38δ modulate innate immune response by regulating MEF2D activation.p38γ 和 p38δ 通过调节 MEF2D 的激活来调节先天免疫反应。
Elife. 2023 Jul 17;12:e86200. doi: 10.7554/eLife.86200.
10
p38γ MAPK Inflammatory and Metabolic Signaling in Physiology and Disease.p38γ MAPK 在生理学和疾病中的炎症和代谢信号转导。
Cells. 2023 Jun 21;12(13):1674. doi: 10.3390/cells12131674.
本文引用的文献
1
Identification of protein phosphorylation sites by a combination of mass spectrometry and solid phase Edman sequencing.通过质谱法和固相埃德曼测序相结合的方法鉴定蛋白质磷酸化位点。
J Biomol Tech. 2002 Sep;13(3):119-30.
2
Intermediate filaments mediate cytoskeletal crosstalk.中间丝介导细胞骨架串扰。
Nat Rev Mol Cell Biol. 2004 Aug;5(8):601-13. doi: 10.1038/nrm1438.
3
Stress- and mitogen-induced phosphorylation of the synapse-associated protein SAP90/PSD-95 by activation of SAPK3/p38gamma and ERK1/ERK2.应激和有丝分裂原通过激活SAPK3/p38γ和ERK1/ERK2诱导突触相关蛋白SAP90/PSD-95发生磷酸化。
Biochem J. 2004 May 15;380(Pt 1):19-30. doi: 10.1042/BJ20031628.
4
PSD93 regulates synaptic stability at neuronal cholinergic synapses.PSD93调节神经元胆碱能突触处的突触稳定性。
J Neurosci. 2004 Jan 14;24(2):378-88. doi: 10.1523/JNEUROSCI.3865-03.2004.
5
Human homolog of disc-large is required for adherens junction assembly and differentiation of human intestinal epithelial cells.人盘状大蛋白同源物是人类肠上皮细胞黏附连接组装和分化所必需的。
J Biol Chem. 2004 Mar 12;279(11):10157-66. doi: 10.1074/jbc.M309843200. Epub 2003 Dec 29.
6
Identification of glycogen synthase as a new substrate for stress-activated protein kinase 2b/p38beta.鉴定糖原合酶为应激激活蛋白激酶2b/p38β的新底物。
Biochem J. 2004 Apr 1;379(Pt 1):133-9. doi: 10.1042/BJ20031559.
7
CaMKII-dependent phosphorylation regulates SAP97/NR2A interaction.钙调蛋白激酶II依赖性磷酸化调节突触相关蛋白97/ NR2A相互作用。
J Biol Chem. 2003 Nov 7;278(45):44745-52. doi: 10.1074/jbc.M303576200. Epub 2003 Aug 21.
8
The invagination of excess surface area by shrinking neurons.神经元收缩导致多余表面积内陷。
Biophys J. 2003 Jul;85(1):223-35. doi: 10.1016/S0006-3495(03)74468-3.
9
Dlg, Scribble and Lgl in cell polarity, cell proliferation and cancer.Dlg、Scribble和Lgl在细胞极性、细胞增殖及癌症中的作用
Bioessays. 2003 Jun;25(6):542-53. doi: 10.1002/bies.10286.
10
Regulatory volume increase is associated with p38 kinase-dependent actin cytoskeleton remodeling in rat kidney MTAL.调节性容积增加与大鼠肾脏髓袢升支粗段中p38激酶依赖性肌动蛋白细胞骨架重塑有关。
Am J Physiol Renal Physiol. 2003 Aug;285(2):F336-47. doi: 10.1152/ajprenal.00003.2003. Epub 2003 Apr 29.
Zotero 插件