更新于：2024-09-19

LAT2

更新于：2024-09-19

基本信息

别名

HSPC046、LAB、LAT2

+ [12]

简介

Involved in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. May also be involved in BCR (B-cell antigen receptor)-mediated signaling in B-cells and FCGR1 (high affinity immunoglobulin gamma Fc receptor I)-mediated signaling in myeloid cells. Couples activation of these receptors and their associated kinases with distal intracellular events through the recruitment of GRB2.

关联

100 项与 LAT2 相关的临床结果

登录后查看更多信息

100 项与 LAT2 相关的转化医学

登录后查看更多信息

0 项与 LAT2 相关的专利（医药）

登录后查看更多信息

480

项与 LAT2 相关的文献（医药）

2024-08-01·Microbial Pathogenesis

Genetic trans-complementation of L-protease fails to rescue the infectious foot-and-mouth disease virus from the Lbpro defective genome

Article

作者: Goud, P Manoj Kumar ; Elango, Subhadra ; Dechamma, H.J. ; Chandra Mohan, S. ; Umapathi, V. ; Krishnaswamy, Narayanan ; Deore, Padmaja Shashikant ; Priyanka, M ; Venkatesan, Gnanavel ; Das, Lekshmi ; Dechamma, H J ; Priyanka, M. ; Chandra Mohan, S ; Umapathi, V

Outbreaks of the foot-and-mouth disease (FMD) have major economic impact on the global livestock industry by affecting the animal health and product safety. L-protease, a non-structural protein of FMDV, is a papain-like cysteine proteinase involved in viral protein processing as well as cleavage of host proteins for promoting the virus growth. FMDV synthesizes two forms of leader proteinase,L^pro (Lab^pro and Lb^pro), where the deletion of Lab^pro is lethal and Lb^pro deletion is reported to be attenuated. Defective replicons have been used by trans-complementing the deleted gene to produce one time replicating virus; thus, the bio-safety procedure can be compromised in the production units. Attempts are made to rescue of ΔLb^proFMDV Asia1 virus by co-expressing the Lb^pro protein carried in pcDNA plasmid. Mutant FMDV cDNA, pAsia-ΔLb^pro, was constructed by PCR mediated mutagenesis using inverse primers. Transfection of BHK-21 cells with in-vitro transcribed RNA from the constructs failed to produce an infective mutant FMDV. Genetic trans- complementation of the Lb^pro, which was done by co-transfecting the pcDNALb^pro plasmid DNA along with the pAsia-ΔLb^pro RNA in BHK-21 cells also failed to produce viable virus. Expression experiments of reporter genes and indirect immune-fluorescence confirmed the production of the viral proteins in wild type FMDV pAsia^WT; however, it was absent in the pAsia-ΔLb^pro indicating that the leaderless virus was unable to produce infectious progeny and infect the cells. Failure to produce virus either by Lb^pro deleted mutant clone or by genetic complementation suggests little chance of reversion of the disabled virus with large deletions of FMDV genome.

2024-06-01·Journal of Food Science

Lactobacillus plantarum isolated from kimchi regulates inflammation by increasing interleukin‐10 secretion by antigen‐presenting cells, leading to diminishing of STAT5 phosphorylation in Th2 cells

Article

作者: Choi, Jee Yeon ; Hyung, Kyeong Eun ; Hwang, Kwang Woo ; Park, So-Young ; Lee, Sanggyu ; Yoo, Hyui Kyeong ; Ham, Ju Eon

AbstractThe relationship between allergic inflammation and gut microbiota has been elucidated, and the effect of probiotics on immune disorders has been studied as well. Identifying the role of probiotics in individual diseases and immune responses and selecting and applying specific microorganisms based on these findings can be an effective strategy for using probiotics. Herein, lactobacilli isolated from kimchi were investigated in depth, focusing on their immune regulatory effects and the mechanisms involved. Lactic acid bacteria (LAB) effectively diminished the increased secretion of T helper 2 cytokines, such as IL‐4, IL‐5, and IL‐13, from ovalbumin (OVA)‐sensitized mouse splenocytes. The gene expression of GATA3, IL‐4, IL‐5, IL‐9, and IL‐13 was confirmed to be regulated by LAB. LAB also suppressed IL‐2 production and STAT5 phosphorylation. An IL‐10‐neutralizing antibody attenuated these effects, indicating that LAB‐induced upregulation of IL‐10 in antigen‐presenting cells was responsible at least partially for the increased IL‐2 production and STAT5 phosphorylation in CD4+ T cells. In conclusion, the current study identified one immunomodulatory mechanism that allows LAB to regulate allergic immune reactions and the potential of LAB from kimchi to modulate various immune reactions.

2024-02-05·Journal of Cell Biology

The dynamic recruitment of LAB proteins senses meiotic chromosome axis differentiation in C. elegans

Article

作者: Li, Jiaxiang ; Sun, Yating ; Gao, Jinmin ; Liu, Mengfei ; Zhao, Li ; Meng, Xiaoqian ; Zhang, Yu ; Zhang, Ruirui ; Zhou, Jun ; Li, Qian ; Wang, Ruoxi ; Tian, Yuqi

During meiosis, cohesin and meiosis-specific proteins organize chromatin into an axis-loop architecture, coordinating homologous synapsis, recombination, and ordered chromosome segregation. However, how the meiotic chromosome axis is assembled and differentiated with meiotic progression remains elusive. Here, we explore the dynamic recruitment of two long arms of the bivalent proteins, LAB-1 and LAB-2, in Caenorhabditis elegans. LAB proteins directly interact with the axis core HORMA complexes and weak interactions contribute to their recruitment. LAB proteins phase separate in vitro, and this capacity is promoted by HORMA complexes. During early prophase, synapsis oppositely regulates the axis enrichment of LAB proteins. After the pachytene exit, LAB proteins switch from a reciprocal localization pattern to a colocalization pattern, and the normal dynamic pattern of LAB proteins is altered in meiotic mutants. We propose that LAB recruitment senses axis differentiation, and phase separation of meiotic structures helps subdomain establishment and accurate segregation of the chromosomes.

项与 LAT2 相关的新闻（医药）

2022-10-26

·生物谷

Nature子刊：浙大叶招明团队揭示化疗导致肿瘤免疫逃逸的机制

这些发现揭示了巨噬细胞和肿瘤细胞之间的相互调节在肿瘤免疫逃逸中起着关键作用，并强调了干预LAT2介导的氨基酸摄取，具有改善癌症治疗效果的潜力。骨肉瘤（Osteosarcoma）是最常见的原发性骨恶性肿瘤。自1970年代以来，化疗显著提高了骨肉瘤患者的总体生存期。目前，手术结合新辅助化疗已经成为骨肉瘤的规范化治疗方法。顺铂、阿霉素、甲氨蝶呤和异环磷酰胺的组合化疗方案也已经使用了几十年。尽管化疗显著提高了骨肉瘤的治疗效果，但骨肉瘤的临床预后仍不理想。约三分之一的骨肉瘤患者对化疗药物反应不佳，容易出现复发和转移，5年生存率仅为5-20%。化疗耐药和免疫逃逸已成为骨肉瘤治疗的主要挑战，因此，需要更有效的策略来提高患者的生存期。 2022年10月23日，浙江大学医学院附属第二医院叶招明教授团队在 Nature Communications 期刊发表了题为：Metabolic control of CD47 expression through LAT2-mediated amino acid uptake promotes tumor immune evasion 的研究论文。该研究揭示了化疗诱导的巨噬细胞吞噬抑制的关键机制，化疗会诱导巨噬细胞分泌IL-18，上调肿瘤细胞的氨基酸转运体LAT2的表达，进而上调CD47表达，抑制巨噬细胞的吞噬作用，导致肿瘤细胞的免疫逃逸。该研究还表明，抑制LAT2可以通过下调肿瘤细胞的CD47表达，增强肿瘤细胞的巨噬细胞浸润和吞噬作用，并使小鼠骨肉瘤对化疗药物阿霉素治疗敏感。这些发现促进了我们对化疗耐药机制的理解，并强调了干预LAT2介导的氨基酸摄取具有增强癌症治疗的潜力。癌细胞免疫逃逸的能力在癌症复发和转移中起着至关重要的作用。尽管化疗药物部分通过刺激免疫系统来清除肿瘤细胞，但越来越多的证据表明，化疗后的肿瘤对抗肿瘤免疫的抵抗力增强。巨噬细胞是骨肉瘤中最丰富的免疫细胞类型，其密度与临床结果之间的关系仍然矛盾。对化疗前骨肉瘤标本的分析显示，巨噬细胞密度增加与转移抑制和转移无进展生存期延长有关，而对化疗后骨肉瘤标本的研究显示，与没有转移的骨肉瘤患者相比，可检测到转移的骨肉瘤患者肿瘤中有更多的巨噬细胞。这些结果表明，在骨肉瘤化疗过程中，癌细胞通过一些未知的机制加强了对巨噬细胞的免疫逃逸。 CD47，是人体中由CD47基因编码的跨膜蛋白，属于免疫球蛋白超家族。自20世纪80年代以来，CD47就被发现在多种人类血液肿瘤及膀胱癌、脑瘤等部分实体瘤中高表达。 2009年，斯坦福大学医学院 Irving Weissman 教授在 Cell 发表论文，表明肿瘤细胞高表达CD47，并通过与巨噬细胞表面的信号调节蛋白α（SIRPα）结合，释放 Don't Eat Me（别吃我）信号，从而防止肿瘤细胞被巨噬细胞吞噬。在骨肉瘤中，CD47在骨肉瘤组织中的表达水平通常高于周围正常组织，CD47的高表达与骨肉瘤患者生存率差相关。通过抑制CD47，激活肿瘤相关巨噬细胞增强了巨噬细胞介导的肿瘤细胞清除，抑制了小鼠骨肉瘤的生长和肺转移。CD47阻断剂在晚期血癌患者中也显示出很有希望的活性。目前正在设计临床试验，以评估抑制CD47是否能增强骨肉瘤患者对其他免疫疗法反应。然而，骨肉瘤细胞中CD47的表达是否在化疗反应中受到调控，从而促进肿瘤免疫逃避，目前尚不清楚。癌细胞需要充足的营养来维持它们的快速生长和增殖。氨基酸转运蛋白对维持癌细胞的高水平代谢和蛋白质合成至关重要。因此，在许多原发性人类肿瘤以及各种癌症细胞系中，观察到了通过上调特定转运体来增强氨基酸的吸收。 L型氨基酸转运体（LATs）是中性氨基酸（如谷氨酰胺和亮氨酸）的主要的不依赖钠离子的运输系统。到目前为止，已经发现了四种LATs（LAT1、LAT2、LAT3和LAT4），阻断LAT1已成为癌症治疗中一个有吸引力的策略。但氨基酸摄取与肿瘤免疫检查点调节之间的关系尚不清楚。在这项研究中，研究团队发现，化疗后的骨肉瘤中CD47上调，且这种上调与患者死亡率相关。从机制上说，化疗促进了巨噬细胞白细胞介素18（IL-18）的分泌，从而上调肿瘤细胞中LAT2的表达，进而大幅增强谷氨酰胺和亮氨酸的摄取，而它们是mTORC1的两种有效刺激因子。亮氨酸水平的增加和谷氨酰胺代谢增强激活了mTORC1和随后的c- Myc介导的CD47转录。LAT2缺失或用LAT抑制剂治疗，可下调肿瘤细胞的CD47表达，增强肿瘤细胞的巨噬细胞浸润和吞噬作用，并使小鼠骨肉瘤对化疗药物阿霉素治疗敏感。这些发现揭示了巨噬细胞和肿瘤细胞之间的相互调节在肿瘤免疫逃逸中起着关键作用，并强调了干预LAT2介导的氨基酸摄取，具有改善癌症治疗效果的潜力。