更新于：2024-09-05

DUSP2

更新于：2024-09-05

基本信息

别名

dual specificity phosphatase 2、Dual specificity protein phosphatase 2、Dual specificity protein phosphatase PAC-1

+ [3]

简介

Dephosphorylates both phosphorylated Thr and Tyr residues in MAPK1, and dephosphorylation of phosphotyrosine is slightly faster than that of phosphothreonine (PubMed:8107850). Can dephosphorylate MAPK1 (By similarity).

关联

100 项与 DUSP2 相关的临床结果

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100 项与 DUSP2 相关的转化医学

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0 项与 DUSP2 相关的专利（医药）

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498

项与 DUSP2 相关的文献（医药）

2024-02-20·European journal of pharmacology

Effects of nitrous oxide and ketamine on electrophysiological and molecular responses in the prefrontal cortex of mice: A comparative study.

Article

作者: Stanislav Rozov ; Roosa Saarreharju ; Stanislav Khirug ; Markus Storvik ; Claudio Rivera ; Tomi Rantamäki

Nitrous oxide (N₂O; laughing gas) has recently reported to produce rapid antidepressant effects, but little is known about the underlying mechanisms. We performed transcriptomics, in situ hybridization, and electrophysiological studies to examine the potential shared signatures induced by 1 h inhalation of 50% N₂O and a single subanesthetic dose of ketamine (10 mg/kg, i.p.) in the medial prefrontal cortex (mPFC) in adult mice. Both treatments similarly affected the transcription of several negative regulators of mitogen-activated protein kinases (MAPKs), namely, dual specificity phosphatases. The effects were primarily located in the pyramidal cells. Notably, the overall effects of N₂O on mRNA expression were much more prominent and widespread compared to ketamine. Ketamine caused an elevation of the spiking frequency of putative pyramidal neurons and increased gamma activity (30-100 Hz) of cortical local field potentials. However, N₂O produced no such effects. Spiking amplitudes and spike-to-local field potential phase locking of putative pyramidal neurons and interneurons in this brain area showed no uniform changes across treatments. Our findings suggest that N₂O and subanesthetic-dose ketamine target MAPK pathway in the mPFC but produce varying electrophysiological responses.

2024-01-22·Briefings in bioinformatics

Enhancing protein dynamics analysis with hydrophilic polyethylene glycol cross-linkers.

Article

作者: Min Sun ; Jing Chen ; Chang Zhao ; Lihua Zhang ; Maili Liu ; Yukui Zhang ; Qun Zhao ; Zhou Gong

Cross-linkers play a critical role in capturing protein dynamics in chemical cross-linking mass spectrometry techniques. Various types of cross-linkers with different backbone features are widely used in the study of proteins. However, it is still not clear how the cross-linkers' backbone affect their own structure and their interactions with proteins. In this study, we systematically characterized and compared methylene backbone and polyethylene glycol (PEG) backbone cross-linkers in terms of capturing protein structure and dynamics. The results indicate the cross-linker with PEG backbone have a better ability to capture the inter-domain dynamics of calmodulin, adenylate kinase, maltodextrin binding protein and dual-specificity protein phosphatase. We further conducted quantum chemical calculations and all-atom molecular dynamics simulations to analyze thermodynamic and kinetic properties of PEG backbone and methylene backbone cross-linkers. Solution nuclear magnetic resonance was employed to validate the interaction interface between proteins and cross-linkers. Our findings suggest that the polarity distribution of PEG backbone enhances the accessibility of the cross-linker to the protein surface, facilitating the capture of sites located in dynamic regions. By comprehensively benchmarking with disuccinimidyl suberate (DSS)/bis-sulfosuccinimidyl-suberate(BS3), bis-succinimidyl-(PEG)2 revealed superior advantages in protein dynamic conformation analysis in vitro and in vivo, enabling the capture of a greater number of cross-linking sites and better modeling of protein dynamics. Furthermore, our study provides valuable guidance for the development and application of PEG backbone cross-linkers.

2024-01-15·Chinese medical journal

Magnesium lithospermate B enhances the potential of human-induced pluripotent stem cell-derived cardiomyocytes for myocardial repair.

Article

作者: Chengming Fan ; Kele Qin ; Chukwuemeka Daniel Iroegbu ; Kun Xiang ; Yibo Gong ; Qing Guan ; Wenxiang Wang ; Jun Peng ; Jianjun Guo ; Xun Wu ; Jinfu Yang

BACKGROUND:

We previously reported that activation of the cell cycle in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) enhances their remuscularization capacity after human cardiac muscle patch transplantation in infarcted mouse hearts. Herein, we sought to identify the effect of magnesium lithospermate B (MLB) on hiPSC-CMs during myocardial repair using a myocardial infarction (MI) mouse model.

METHODS:

In C57BL/6 mice, MI was surgically induced by ligating the left anterior descending coronary artery. The mice were randomly divided into five groups (n = 10 per group); a MI group (treated with phosphate-buffered saline only), a hiPSC-CMs group, a MLB group, a hiPSC-CMs + MLB group, and a Sham operation group. Cardiac function and MLB therapeutic efficacy were evaluated by echocardiography and histochemical staining 4 weeks after surgery. To identify the associated mechanism, nuclear factor (NF)-κB p65 and intercellular cell adhesion molecule-1 (ICAM1) signals, cell adhesion ability, generation of reactive oxygen species, and rates of apoptosis were detected in human umbilical vein endothelial cells (HUVECs) and hiPSC-CMs.

RESULTS:

After 4 weeks of transplantation, the number of cells that engrafted in the hiPSC-CMs + MLB group was about five times higher than those in the hiPSC-CMs group. Additionally, MLB treatment significantly reduced tohoku hospital pediatrics-1 (THP-1) cell adhesion, ICAM1 expression, NF-κB nuclear translocation, reactive oxygen species production, NF-κB p65 phosphorylation, and cell apoptosis in HUVECs cultured under hypoxia. Similarly, treatment with MLB significantly inhibited the apoptosis of hiPSC-CMs via enhancing signal transducer and activator of transcription 3 (STAT3) phosphorylation and B-cell lymphoma-2 (BCL2) expression, promoting STAT3 nuclear translocation, and downregulating BCL2-Associated X, dual specificity phosphatase 2 (DUSP2), and cleaved-caspase-3 expression under hypoxia. Furthermore, MLB significantly suppressed the production of malondialdehyde and lactate dehydrogenase and the reduction in glutathione content induced by hypoxia in both HUVECs and hiPSC-CMs in vitro.

CONCLUSIONS:

MLB significantly enhanced the potential of hiPSC-CMs in repairing injured myocardium by improving endothelial cell function via the NF-κB/ICAM1 pathway and inhibiting hiPSC-CMs apoptosis via the DUSP2/STAT3 pathway.

项与 DUSP2 相关的新闻（医药）

2022-09-19

·佰傲谷BioValley

JAK-STAT通路与肿瘤免疫

30年前，JAK-STAT通路被人们发现，之后在转化与应用方面被持续关注。在细胞因子刺激下，这条通路调控着体内多种生物学活动、介导了几乎所有的免疫反应，不仅是免疫防御，还包括促进肿瘤细胞存活、免疫逃逸以及持续性炎症（特应性皮炎）的过程。JAK-STAT简介非受体酪氨酸激酶（JAK），包括JAK1/2/3和Tyk2。信号转导及激活转录因子（STAT），包括STAT1/2/3/4/5a/5b/6。细胞因子是JAK-STAT的主要激活信号，通过与膜上受体结合，使JAKs激活并介导STAT磷酸化入核，以调控靶基因的转录。细胞因子信号 → 激活JAK → STAT磷酸化后入核 → 调控转录Signal Transduct Target Ther. 2021 Nov 26;6(1):402. JAK-STAT与肿瘤免疫在不同的刺激信号下，JAK-STAT通路能够介导产生不同的效应，根据TME中的多种信号，发挥出抗肿瘤和促肿瘤双重作用。1. 抗肿瘤功能在多种细胞中，STAT-JAK都会响应抗瘤信号。在NK细胞中IFN-α/β信号：通过STAT1、STAT2介导NK细胞免疫应答。IL-2、IL-15信号：通过STAT5信号维持NK细胞稳态、增殖、功能。IL-12信号：通过STAT1、STAT3、STAT4使NK细胞产生INF-γ、穿孔素、颗粒酶介导细胞毒性。在T细胞中IFNα/β信号：通过STAT4促进抗原相关CD8T细胞扩增和细胞毒性作用。IL-12和IFN-γ信号：通过STAT1、STAT4诱导T-BET产生，能够促进T细胞进一步分泌IFN-γ。并且还能促进T细胞向Th1细胞分化，阻止向Th2、Th17、Treg等免疫抑制性亚群分化。细胞死亡后通过触发JAK-STAT信号以刺激IRG的TLR感测，能够与TCR协同增强T细胞分泌细胞因子。在肿瘤细胞中IFN-γ作用于与肿瘤细胞，通过STAT1激活caspase-1/3/8和FAS，从而诱导肿瘤细胞凋亡。2. 促肿瘤功能响应促瘤信号的主要为STAT3和STAT5。STAT3是响应促瘤信号的主要转录因子。生长因子、多种细胞因子、集落刺激因子IL-6是STAT3最主要的激活信号：通过介导IL-6-gp130与IL-6-IL-60这两个复合体形成，进而驱动肿瘤细胞以JAK-STAT依赖性的跨内皮迁移。IL-10能够通过STAT3抑制APC细胞阻断T细胞功能，促进Treg细胞分化。IL-6、IL-10导致STAT3表达升高，而升高的STAT3能够通过正反馈环路进一步促进IL-6、IL-10分泌，最终导致利于肿瘤生长环境的形成。此外，在STAT3信号激活后还能够抑制STAT1、IRF7、IRF9基因的表达，从而抑制Ⅰ型IFN信号，最终也促进免疫抑制性TME形成。STAT5在乳腺癌和前列腺癌中，STAT5与Foxp3结合，能够维持其过表达的同时促进Treg细胞发育。IL-8通过激活过表达的STAT5与乳腺癌细胞存活、化疗耐药以及转移有关。与STAT3一样，过度激活的STAT5也能够抑制IFNα信号对STAT1的激活，影响下游反应。3. 负性调节信号在JAK-STAT通路中，为了维持正确的信号传递，各层面存在多种稳态调控机制，包括负调控信号。负调控因子同样具有促瘤与抗瘤双重作用。SOCS1是维持T细胞稳态的细胞因子信号转导抑制物。它能够结合并促进JAK与STAT分解，在STAT激活时SOCS的快速诱导是决定JAK-STAT信号强度的关键。其表达缺失与肿瘤细胞PD-L1高表达有关。PIAS是细胞因子激活的STAT蛋白抑制物，能够物理阻断核内激活的STAT与DNA结合，从而阻止信号诱导。PIAS1能够抑制Ⅰ/Ⅱ型IFN→STAT1信号传递，在多种恶心肿瘤中表达升高。PIAS3被沉默时，会导致STAT3过度激活。PTP蛋白质酪氨酸磷酸酶，包括SHP1/2、DUSP2、CD45。能够去磷酸化JAK, STAT上的酪氨酸残基，以促进它们快速地重新激活。SHP1通过抑制STAT3和NFκB信号在肝癌中发挥抗瘤作用。SHP2抑制剂与PD-1抑制剂联用能够发挥短暂的抗瘤反应。小结JAK-STAT通路看似是一个简单的线性过程，但在信号传递过程中通路上的所有成员都会参与调控。通路中复杂调控机制的存在，使STAT及辅助分子表达、结构、功能方面的微小改动就可以对免疫信号和肿瘤进展产生深远的影响。推荐阅读IL-6：肿瘤炎症、癌症转移核心分子参考资料Hu X et al. The JAK/STAT signaling pathway: from bench to clinic. Signal Transduct Target Ther. 2021 Nov 26;6(1):402. Yu H et al. Revisiting STAT3 signalling in cancer: new and unexpected biological functions. Nat Rev Cancer. 2014 Nov;14(11):736-46. Thomas SJ et al. The role of JAK/STAT signalling in the pathogenesis, prognosis and treatment of solid tumours. Br J Cancer. 2015 Jul 28;113(3):365-71.Kiu H et al. Biology and significance of the JAK/STAT signalling pathways. Growth Factors. 2012 Apr;30(2):88-106.Niu GJ et al. Protein Inhibitor of Activated STAT (PIAS) Negatively Regulates the JAK/STAT Pathway by Inhibiting STAT Phosphorylation and Translocation. Front Immunol. 2018 Oct 26;9:2392.Zhao M et al. SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade. Acta Pharm Sin B. 2019 Mar;9(2):304-315.