更新于：2024-09-19

PTPRJ

更新于：2024-09-19

基本信息

别名

CD148、Density-enhanced phosphatase 1、DEP-1

+ [10]

简介

Tyrosine phosphatase which dephosphorylates or contributes to the dephosphorylation of CTNND1, FLT3, PDGFRB, MET, KDR, LYN, SRC, MAPK1, MAPK3, EGFR, TJP1, OCLN, PIK3R1 and PIK3R2 (PubMed:10821867, PubMed:12062403, PubMed:12370829, PubMed:12475979, PubMed:18348712, PubMed:19494114, PubMed:19922411, PubMed:21262971). Plays a role in cell adhesion, migration, proliferation and differentiation (PubMed:12370829, PubMed:14709717, PubMed:16682945, PubMed:19836242). Involved in vascular development (By similarity). Regulator of macrophage adhesion and spreading (By similarity). Positively affects cell-matrix adhesion (By similarity). Positive regulator of platelet activation and thrombosis. Negative regulator of cell proliferation (PubMed:16682945). Negative regulator of PDGF-stimulated cell migration; through dephosphorylation of PDGFR (PubMed:21091576). Positive regulator of endothelial cell survival, as well as of VEGF-induced SRC and AKT activation; through KDR dephosphorylation (PubMed:18936167). Negative regulator of EGFR signaling pathway; through EGFR dephosphorylation (PubMed:19836242). Enhances the barrier function of epithelial junctions during reassembly (PubMed:19332538). Negatively regulates T-cell receptor (TCR) signaling (PubMed:9531590, PubMed:9780142, PubMed:11259588). Upon T-cell TCR activation, it is up-regulated and excluded from the immunological synapses, while upon T-cell-antigen presenting cells (APC) disengagement, it is no longer excluded and can dephosphorylate PLCG1 and LAT to down-regulate prolongation of signaling (PubMed:11259588, PubMed:12913111).

关联

项与 PTPRJ 相关的药物

Anti-CD148 mAb (Amgen)

靶点

PTPRJ

作用机制

PTPRJ抑制剂

在研机构-

原研机构

Immunex Corp.

在研适应症-

非在研适应症

肿瘤 [+1]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 PTPRJ 相关的临床结果

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100 项与 PTPRJ 相关的转化医学

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0 项与 PTPRJ 相关的专利（医药）

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373

项与 PTPRJ 相关的文献（医药）

2024-12-01·Rice

The DEP1 Mutation Improves Stem Lodging Resistance and Biomass Saccharification by Affecting Cell Wall Biosynthesis in Rice

Article

作者: Cao, Liyu ; Wang, Meihan ; Yin, Xuelin ; Yan, Xia ; Ruan, Nan ; Wang, Ye ; Xu, Quan ; Li, Fengcheng ; Dang, Zhengjun ; Yang, Xiao ; Chen, Kaixuan ; Tian, Fuhao ; Huang, Yuwei

Abstract: Background: Plant cell walls have evolved precise plasticity in response to environmental stimuli.The plant heterotrimeric G protein complexes could sense and transmit extracellular signals to intracellular signaling systems, and activate a series of downstream responses. dep1 (Dense and Erect Panicles 1), the gain-of-function mutation of DEP1 encoding a G protein γ subunit, confers rice multiple improved agronomic traits.However, the effects of DEP1 on cell wall biosynthesis and wall-related agronomic traits remain largely unknown.Results: In this study, we showed that the DEP1 mutation affects cell wall biosynthesis, leading to improved lodging resistance and biomass saccharification.The DEP1 is ubiquitously expressed with a relatively higher expression level in tissues rich in cell walls.The CRISPR/Cas9 editing mutants of DEP1 (dep1-cs) displayed a significant enhancement in stem mech. properties relative to the wild-type, leading to a substantial improvement in lodging resistance.Cell wall analyses showed that the DEP1 mutation increased the contents of cellulose, hemicelluloses, and pectin, and reduced lignin content and cellulose crystallinity (CrI).Addnl., the dep1-cs seedlings exhibited higher sensitivity to cellulose biosynthesis inhibitors, 2,6-Dichlorobenzonitrile (DCB) and isoxaben, compared with the wild-type, confirming the role of DEP1 in cellulose deposition.Moreover, the DEP1 mutation-mediated alterations of cell walls lead to increased enzymic saccharification of biomass after the alkali pretreatment.Furthermore, the comparative transcriptome anal. revealed that the DEP1 mutation substantially altered expression of genes involved in carbohydrate metabolism, and cell wall biosynthesis.Conclusions: Our findings revealed the roles of DEP1 in cell wall biosynthesis, lodging resistance, and biomass saccharification in rice and suggested genetic modification of DEP1 as a potential strategy to develop energy rice varieties with high lodging resistance.

2024-09-01·Plant Physiology and Biochemistry

Melatonin differentially refines the metabolome to improve seed formation during grain developmental stages and enhances yield in two contrasting rice cultivars, grown in arsenic-contaminated soil

Article

作者: Roychoudhury, Aryadeep ; Samanta, Santanu ; Banerjee, Aditya

The manuscript revealed the ameliorative effects of exogenous melatonin in two distinct reproductive stages, i.e., developing grains (20 days after pollination) and matured grains (40 days after pollination) in two contrasting indica rice genotypes, viz., Khitish (arsenic-susceptible) and Muktashri (arsenic-tolerant), irrigated with arsenic-contaminated water throughout their life-cycle. Melatonin administration improved yield-related parameters like rachis length, primary and secondary branch length, number of grains per panicle, number of filled and empty grains per panicle, grain length and breadth and 1000-grain per weight. Expression of GW2, which negatively regulates grain development, was suppressed, along with concomitant induction of positive regulators like GIF1, DEP1 and SPL14 in both Khitish and Muktashri. Melatonin lowered arsenic bioaccumulation in grains and tissue biomass, more effectively in Khitish. Unregulated production of reactive oxygen species, leading to cellular necrosis caused by arsenic, was reversed in presence of melatonin. Endogenous melatonin level was stimulated due to up-regulation of the key biosynthetic genes, SNAT and ASMT. Melatonin enhanced the production of diverse antioxidants like anthocyanins, flavonoids, total phenolics and ascorbic acid and also heightened the production of thiol-metabolites (cysteine, reduced glutathione, non-protein thiols and phytochelatin), ensuring effective chelation and arsenic detoxification. Altogether, our observation, supported by principal component analysis, proved that melatonin re-programs the antioxidative metabolome to enhance plant resilience against arsenic stress to mitigate oxidative damages and reduce arsenic translocation from the soil to tissue biomass and edible grains.

2024-06-01·Molecular & Cellular Proteomics

Quantitative Proteomic Analysis Reveals Functional Alterations of the Peripheral Immune System in Colorectal Cancer

Article

作者: Ji, Jianguo ; Zhu, Wenyuan ; Wang, Qingsong ; Shen, Jian ; Li, Minzhe

Colorectal cancer (CRC) is characterized by high morbidity, high mortality, and limited response to immunotherapies. The peripheral immune system is an important component of tumor immunity, and enhancements of peripheral immunity help to suppress tumor progression. However, the functional alterations of the peripheral immune system in CRC are unclear. Here, we used mass spectrometry-based quantitative proteomics to establish a protein expression atlas for the peripheral immune system in CRC, including plasma and five types of immune cells (CD4⁺ T cells, CD8⁺ T cells, monocytes, natural killer cells, and B cells). Synthesizing the results of the multidimensional analysis, we observed an enhanced inflammatory phenotype in CRC, including elevated expression of plasma inflammatory proteins, activation of the inflammatory pathway in monocytes, and increased inflammation-related ligand-receptor interactions. Notably, we observed tumor effects on peripheral T cells, including altered cell subpopulation ratios and suppression of cell function. Suppression of CD4⁺ T cell function is mainly mediated by high expression levels of protein tyrosine phosphatases. Among them, the expression of protein tyrosine phosphatase receptor type J (PTPRJ) gradually increased with CRC progression; knockdown of PTPRJ in vitro could promote T cell activation, thereby enhancing peripheral immunity. We also found that the combination of leucine-rich α-2 glycoprotein 1 (LRG1) and apolipoprotein A4 (APOA4) had the best predictive ability for colorectal cancer and has the potential to be a biomarker. Overall, this study provides a comprehensive understanding of the peripheral immune system in CRC. It also offers insights regarding the potential clinical utilities of these peripheral immune characteristics as diagnostic indicators and therapeutic targets.

项与 PTPRJ 相关的新闻（医药）

2023-04-23

·生物制品圈

新发现！西湖大学施一公团队揭示SIN3组蛋白去乙酰化酶复合物的两种组装模式

导读：SIN3-HDAC(组蛋白去乙酰化酶)复合物在促进局部组蛋白去乙酰化以调节染色质可及性和基因表达方面具有重要作用。针对不同的染色质区域，有两种主要类型的SIN3 / HDAC复合物（称为SIN3L和SIN3S）。近日，西湖大学施一公团队占谢超及王程程在《Cell Discovery》期刊上发表了一篇题为“Two assembly modes for SIN3 histone deacetylase complexes”的研究论文，该研究揭示了SIN3组蛋白去乙酰化酶复合物的两种组装模式。https://www-nature-com.libproxy1.nus.edu.sg/articles/s41421-023-00539-x研究背景 01 在SIN3L的结构中，每个Sin3亚型（Pst1和Pst3）与一个组蛋白去乙酰化酶Clr6和一个含WD40的蛋白质Prw1相互作用，形成两个裂片。这两个瓣分别由来自Sds3/Dep1和Rxt2/Png2的两个垂直线圈域桥接。在SIN3S的结构中，只有一个叶瓣由另一个Sin3亚型Pst2组织的裂片;每个 Cph1 和 Cph2 都与 Eaf3 分子结合，为组蛋白识别和结合提供两个模块。值得注意的是，SIN3L中的Pst1叶和SIN3S中的Pst2叶具有相似的构象，其脱乙酰酶活性位点暴露在空间中; 然而，SIN3L中的Pst3瓣处于致密状态，其活动中心埋在内部并被阻塞。研究发现 02 本工作确定了S. pombe的SIN3L和SIN3S配合物的原子结构，揭示了SIN3 / HDAC配合物的两种代表性组织机制。结合结构分析和以前的报告，研究人员发现SIN3L和SIN3S的不同组装模式有助于HDAC靶向不同的染色质区域。来自Pst3-Flag菌株的内源性纯化的SIN3L样品含有一组DNA结合蛋白，包括铁感应转录阻遏因子Fep1、起始对照蛋白Cdc10、细胞分裂周期相关蛋白Res1/2、前mRNA加工因子Prp39和其他转录因子（包括Atf1、Nrm1、P14E8.02等），这些因子在Pst2-Flag菌株的SIN3S样品中不存在。在SIN3L复合物中，Pst1/3的PAH1/2结构域被认为与转录因子相互作用。此外，SIN3L复合物还为染色质识别提供了其他结构域，例如Png2的PHD。据报道，酵母 SIN3S 复合物可识别 H3K36me3 标记物并在基因编码区发挥作用，以抑制反义转录并保护免受基因毒性试剂的侵害。Pst2的PAH1/2结构域与Pst1/3不同，与Cph1和Cph2相互作用，将HB1和HB2连接到Pst2瓣。在SIN3S的结构中，研究人员发现HB1和HB2采用不同的取向。HB2中的Cph2_PHD1与活性位点相邻;而HB1中的Cph1_PHD与活性位点之间的距离长度高达80 Å。研究人员意识到酿酒酵母SIN3S（也称为Rpd3S）复合物优先结合二核小体。因此，研究人员假设SIN3S复合物的HB1和HB2可能为相邻的核小体提供两个结合位点。但它需要进一步的研究来证实。此外，之前表明I类HDAC复合物（包括SIN3，NuRD，SMART，CoREST，MiDAC等）需要两种脱乙酰酶。并且发现两个HDAC分子在人类NuRD亚复合物的结构中对称和MiDAC亚复合体。在这项研究中表明，SIN3L复合物包含两个不对称脱乙酰酶活性位点，而SIN3S复合物只有一个。这些发现为I类HDAC复合物的多样化和复杂的分子机制提供了新的思路。另外，基于序列守恒分析，研究人员将人类癌症突变数据库中的不变残基子集映射到SIN3L / SIN3S模型。S.pombe SIN3L和SIN3复合物的结构测定研究意义 03 简而言之，本研究工作揭示了SIN3 / HDAC复合物实现特异性靶向的两种经典组织机制，并为研究组蛋白去乙酰化酶复合物提供了框架。参考资料：https://www-nature-com.libproxy1.nus.edu.sg/articles/s41421-023-00539-x

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