更新于：2024-05-01

LCK

酪氨酸蛋白激酶LCK

更新于：2024-05-01

基本信息

别名

淋巴细胞特异性蛋白酪氨酸激酶p56（lck）、LCK、LCK proto-oncogene, Src family tyrosine kinase

+ [9]

简介

Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP. Interacts with FYB2 (PubMed:27335501).

关联

项与 LCK 相关的药物

Pazopanib Hydrochloride

培唑帕尼

靶点

FGFR1 x FGFR3 x Flt3L x ITK x LCK x PDGFRα x PDGFRβ x VEGFR1 x VEGFR2 x VEGFR3 x c-Kit

作用机制

FGFR1拮抗剂 [+10]

在研机构

Novartis Europharm Ltd. [+5]

原研机构

GSK Plc

在研适应症

肾细胞癌 [+6]

非在研适应症

前列腺腺癌 [+104]

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2009-10-19

Pirfenidone

吡非尼酮

靶点

CCL2 x IL-10 x IL-6 x IL1 x TNF-α

作用机制

CSF-1R拮抗剂 [+13]

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段批准上市

首次获批国家/地区

日本

首次获批日期2008-10-16

Dasatinib

达沙替尼

靶点

Bcr-Abl x EphA2 x FYN x LCK x PDGFRβ x Protein-tyrosine kinases x SRC x YES1 x c-Kit

作用机制

Bcr-Abl抑制剂 [+8]

在研机构

Bristol Myers Squibb Co. [+5]

原研机构

Bristol Myers Squibb Co.

在研适应症

费城染色体阳性急性淋巴细胞白血病 [+21]

非在研适应症

腺泡细胞癌 [+61]

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2006-06-28

1,026

项与 LCK 相关的临床试验

NCT04199026 / Not yet recruiting早期临床1期IIT

Pilot Trial of an Implantable Microdevice for In Vivo Drug Sensitivity Testing in Patients With Sarcomas

This early phase I trial studies the side effects of implanting and removing a microdevice in patients with sarcomas that have spread to other places in the body (metastatic) or have come back (recurrent). Microdevices are rice-sized devices that are implanted into tumor tissue and are loaded with 10 different drugs that are delivered at very small doses, or "microdoses," which may only affect a very small, local area inside the tumor. The purpose of this study is to determine which drugs delivered in the microdevice affect tumor tissue in patients with sarcomas.

开始日期2025-01-31

申办/合作机构

The University of Texas MD Anderson Cancer Center

[+1]

NCT05638763 / Recruiting临床2期IIT

Cytochrome P450 Inhibition With Ketoconazole to Decrease Dosage and Costs of Dasatinib for Chronic Myelogenous Leukemia

This phase 2 single-arm study aims to demonstrate the efficacy of strong cytochrome inhibition with ketoconazole to reduce dasatinib dosage for adults with chronic myelogenous leukemia. Researchers will describe response rates and adverse events.

开始日期2024-11-01

申办/合作机构

Hospital Universitario. Dr. José Eleuterio González

NCT06241560 / Not yet recruiting临床2期

An Open-label, Single-group Trial to Evaluate the Effect of Pirfenidone on the Pharmacokinetics of a Single Oral Dose of BI 1015550

This study is open to adults with idiopathic pulmonary fibrosis (IPF) who are 40 years and older. The purpose of this study is to find out whether a medicine called pirfenidone changes the amount of a medicine called BI 1015550 in the blood. Some people may take more than one medicine at a time. Therefore, it is important to understand how different medicines influence one another.
Participants take one dose of BI 1015550 as a tablet. Participants then take one tablet of pirfenidone 3 times a day for one week. The dose is then increased to 2 tablets 3 times a day for the second week. In the third week the dose is increased further to 3 tablets 3 times a day. Participants then take another dose of BI 1015550 as a tablet.
Participants are in the study for a little over 1 month. During this time, they visit the study site 15 times. Two of the visits include overnight stays at the study site. The study staff also contacts the participants by phone. During the visits, the doctors collect information about participants' health and take blood samples from the participants. They compare the amount of pirfenidone and BI 1015550 in the blood. Doctors also regularly check participants' health and take note of any unwanted effects.

开始日期2024-08-06

申办/合作机构

Boehringer Ingelheim GmbH

100 项与 LCK 相关的临床结果

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100 项与 LCK 相关的转化医学

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0 项与 LCK 相关的专利（医药）

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3,630

项与 LCK 相关的文献（医药）

2024-03-04·The Journal of experimental medicine

TCR signaling induces STAT3 phosphorylation to promote TH17 cell differentiation.

Article

作者: Zhen Qin ; Ruining Wang ; Ping Hou ; Yuanyuan Zhang ; Qianmu Yuan ; Ying Wang ; Yuedong Yang ; Tao Xu

TH17 differentiation is critically controlled by "signal 3" of cytokines (IL-6/IL-23) through STAT3. However, cytokines alone induced only a moderate level of STAT3 phosphorylation. Surprisingly, TCR stimulation alone induced STAT3 phosphorylation through Lck/Fyn, and synergistically with IL-6/IL-23 induced robust and optimal STAT3 phosphorylation at Y705. Inhibition of Lck/Fyn kinase activity by Srci1 or disrupting the interaction between Lck/Fyn and STAT3 by disease-causing STAT3 mutations selectively impaired TCR stimulation, but not cytokine-induced STAT3 phosphorylation, which consequently abolished TH17 differentiation and converted them to FOXP3+ Treg cells. Srci1 administration or disrupting the interaction between Lck/Fyn and STAT3 significantly ameliorated TH17 cell-mediated EAE disease. These findings uncover an unexpected deterministic role of TCR signaling in fate determination between TH17 and Treg cells through Lck/Fyn-dependent phosphorylation of STAT3, which can be exploited to develop therapeutics selectively against TH17-related autoimmune diseases. Our study thus provides insight into how TCR signaling could integrate with cytokine signal to direct T cell differentiation.

2024-02-24·Psychopharmacology

Dorsal hippocampal astrocytes mediate the development of heroin withdrawal-enhanced fear learning.

Article

作者: Shveta V Parekh ; Lydia O Adams ; Gillian A Barkell ; Jacqueline E Paniccia ; Kathryn J Reissner ; Donald T Lysle

There is a significant co-occurrence of opioid use disorder (OUD) and post-traumatic stress disorder (PTSD) in clinical populations. However, the neurobiological mechanisms linking chronic opioid use, withdrawal, and the development of PTSD are poorly understood. Our previous research has shown that proinflammatory cytokines, expressed primarily by astrocytes in the dorsal hippocampus (DH), play a role in the development of heroin withdrawal-enhanced fear learning (HW-EFL), an animal model of PTSD-OUD comorbidity. Given the role of astrocytes in memory, fear learning, and opioid use, our experiments aimed to investigate their involvement in HW-EFL. Experiment 1 examined the effect of withdrawal from chronic heroin administration on GFAP surface area and volume, and identified increased surface area and volume of GFAP immunoreactivity in the dentate gyrus (DG) following 24-hour heroin withdrawal. Experiment 2 examined astrocyte morphology and synaptic interactions at the 24-hour withdrawal timepoint using an astroglial membrane-bound GFP (AAV5-GfaABC1D-lck-GFP). Although we did not detect significant changes in surface area and volume of GfaABC1D-Lck-GFP labelled astrocytes, we did observe a significant increase in the colocalization of astrocyte membranes with PSD-95 (postsynaptic density protein 95) in the DG. Experiment 3 tested if stimulating astroglial G_i signaling in the DH alters HW-EFL, and our results demonstrate this manipulation attenuates HW-EFL. Collectively, these findings contribute to our current understanding of the effects of heroin withdrawal on astrocytes and support the involvement of astrocytes in the comorbid relationship between opioid use and anxiety disorders.

2024-02-20·Journal of biomolecular structure & dynamics

Integrating network pharmacology, molecular docking and simulation approaches with machine learning reveals the multi-target pharmacological mechanism of Berberis integerrima against diabetic nephropathy.

Review

作者: Xueqin Zhang ; Peng Chao ; Lei Zhang ; Jinyu Lu ; Aiping Yang ; Hong Jiang ; Chen Lu

Diabetic nephropathy (DN) is one of the most feared complications of diabetes and key cause of end-stage renal disease (ESRD). Berberis integerrima has been widely used to treat diabetic complications, but exact molecular mechanism is yet to be discovered. Data on active ingredients of B. integerrima and target genes of both diabetic nephropathy and B.integerrima were obtained from public databases. Common results between B. integerrima and DN targets were used to create protein-protein interaction (PPI) network using STRING database and exported to Cytoscape software for the selection of hub genes based on degree of connectivity. Future, PPI network between constituents and overlapping targets was created using Cytoscape to investigate the network pharmacological effects of B. integerrima on DN. KEGG pathway analysis of core genes exposed their involvement in excess glucose-activated signaling pathway. Then, expression of core genes was validated through machine learning classifiers. Finally, PyRx and AMBER18 software was used for molecular docking and simulation. We found that Armepavine, Berberine, Glaucine, Magnoflorine, Reticuline, Quercetin inhibits the growth of diabetic nephropathy by affecting ICAM1, PRKCB, IKBKB, KDR, ALOX5, VCAM1, SYK, TBXA2R, LCK, and F3 genes. Machine learning revealed SYK and PRKCB as potential genes that could use as diagnostic biomarkers against DN. Furthermore, docking and simulation analysis showed the binding affinity and stability of the active compound with target genes. Our study revealed that B. integerrima has preventive effect on DN by acting on glucose-activated signaling pathways. However, experimental studies are needed to reveal biosafety profiles of B. integerrima in DN.Communicated by Ramaswamy H. Sarma.

项与 LCK 相关的新闻（医药）

2024-02-07

·今日头条

中山大学唐玲珑团队最新发现：揭示鼻咽癌诱导化疗耐药分子机制

本文为转化医学网原创，转载请注明出处作者：Leung 导读：研究结果表明，转录因子ATMIN在鼻咽癌中作为耐药基因发挥功能。 2024年2月6日，中山大学唐玲珑和赵银共同通讯在期刊 Cell Death & Disease上发表题为“Transcription factor ATMIN facilitates chemoresistance in nasopharyngeal carcinoma”的研究论文。研究结果表明，转录因子ATMIN在鼻咽癌中作为耐药基因发挥功能。机制上，去泛素化酶USP10通过去除ATMIN泛素化稳定ATMIN蛋白水平，ATMIN进一步转录激活LCK促进鼻咽癌生长增殖和多西他赛耐药。本研究揭示了USP10-ATMIN-LCK信号轴在调控鼻咽癌生长增殖和多西他赛敏感性中的分子机制，为鼻咽癌的治疗提供了潜在靶点。 https://doi.org/10.1038/s41419-024-06496-x 研究背景 01 鼻咽癌是一种恶性头颈部肿瘤，在东亚和东南亚，特别是中国南部地区发病率较高。既往III期临床试验表明，“多西他赛-顺铂-5氟尿嘧啶(TPF)”诱导化疗可显著提高中晚期鼻咽癌患者生存率。因此，TPF诱导化疗被推荐作为中晚期鼻咽癌患者的一线治疗方案。然而，临床上并非所有患者均能从TPF诱导化疗中获益。接近10%的患者在接受TPF诱导化疗后肿瘤无应答，预后差。因此，当前亟需阐明TPF化疗耐药的分子机制，挖掘潜在治疗靶点。转录因子是序列特异性的DNA结合蛋白，通过识别并结合靶基因的顺式调节元件来控制基因的转录和表达。到目前为止，约20%的癌基因被报道为转录因子，它们在肿瘤的发生发展、转移和治疗反应中发挥着重要作用。然而，转录因子在鼻咽癌中的作用仍未得到充分阐明，特别是在鼻咽癌诱导化疗耐药中的功能和机制尚不清楚。研究发现 02 通过分析接受过TPF诱导化疗的鼻咽癌患者的基因表达数据和生存信息，我们发现转录因子ATMIN在TPF诱导化疗无应答患者中表达上调，且与不良预后相关。GSEA分析发现多西他赛耐药和生长增殖相关的基因集在ATMIN高表达的鼻咽癌患者中富集。体内外功能实验表明，敲减ATMIN可抑制鼻咽癌细胞生长增殖，并增强其对多西他赛的敏感性。机制上，Co-IP、质谱分析、免疫荧光等实验发现去泛素化酶USP10通过去泛素化稳定ATMIN蛋白水平，是ATMIN在鼻咽癌中表达上调的潜在机制之一。ChIP-Seq和RNA-Seq分析提示ATMIN参与调控细胞死亡通路，并筛选出ATMIN转录调控的10个潜在下游靶基因。ChIP-PCR、双荧光素酶报告实验、功能回补实验进一步证实ATMIN通过转录激活靶基因LCK促进鼻咽癌生长增殖和多西他赛耐药。敲减ATMIN在体内抑制鼻咽癌生长增殖、增强多西他赛敏感性研究结果 03 综上所述，本研究明确了转录因子ATMIN在鼻咽癌中作为耐药基因发挥功能，并阐明了USP10-ATMIN-LCK信号轴促进鼻咽癌生长增殖和多西他赛耐药的分子机制，有望为鼻咽癌患者提供潜在治疗靶点。参考资料： https://doi.org/10.1038/s41419-024-06496-x 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。唐玲珑教授简介教授，主任医师，博士生导师，中山大学肿瘤防治中心放疗科副主任、党支部书记，教育部长江学者特聘教授，华南恶性肿瘤防治全国重点实验室PI。主要从事鼻咽癌的临床及转化研究。近5年来，作为第一或通讯（含共同）作者发表SCI论文28篇，包括JAMA 、Lancet、Lancet Oncol、BMJ、J Clin Oncol（2篇）等，2篇论文入选ESI高被引论文，主持国家自然科学基金面上项目3项。学术兼职包括中国抗癌协会青年理事会理事、广东省抗癌协会鼻咽癌专业青年委员会主任委员，中国抗癌协会鼻咽癌专委会委员及中国肿瘤学会鼻咽癌专委会委员。因团队发展需要，现招聘特聘副研究员1名、博士后2名和技术员2名，感兴趣的老师同学请发邮件至唐玲珑教授邮箱tangll@sysucc.org.cn。热门·直播/活动 🕓 上海｜3月01日-02日 ▶第三届长三角单细胞组学技术应用论坛暨空间组学前沿论坛将在上海召开，诚邀您的参与！点击对应文字查看详情

临床3期基因疗法放射疗法

2024-02-04

·生物制药小编

代谢调控T细胞活化结果

T细胞活化主要包括三段信号：第一信号TCR-MHC、第二信号共刺激和第三信号细胞因子信号转导。大量的证据表明，T细胞的反应在很大程度上依赖于代谢产物的可及性。并且代谢物会通过营养感知和其他机制传递自己的信号。代谢在T细胞活化中的作用：①代谢物不仅是T细胞活化每一个阶段中的基本媒介，而且还提供各自的离散信号来控制T细胞的激活。②代谢物并不只是简单地传播核心T细胞信号，而是将它们自己的偏向传递给CD4+和CD8+ T细胞反应的功能结果。代谢物与T细胞免疫的相互作用不是中性的，某些代谢物的功能偏向决定了T细胞的激活。Nat Immunol.（一）代谢调节TCR信号氨基酸的可获得性会调节TCR的激活和免疫突触的形成。例如：细胞外天冬酰胺水平的增加提高了CD8+T细胞的激活初期和抗肿瘤细胞的效应功能。激活的T细胞对精氨酸的摄取比初始T细胞高得多，细胞内的精氨酸储存在T细胞激活后迅速代谢，从而影响T细胞存活和抗肿瘤功能。T细胞激活过程中会通过Myc20依赖而增加对谷氨酰胺的摄取。在中心，近端抗原特异性信号则被天冬酰胺增强，天冬酰胺促进LCK活性，而镁离子帮助LFA-1进入其活性构象，从而促进与靶细胞更强的附着。不过T细胞在激活过程中对氨基酸的代谢需求通常是时间依赖性的。此外，ROS可降低SHP1的活化，从而促进近端TCR信号强度。肌动蛋白细胞骨架重排则受到溶血磷脂酸和GML等几种代谢物的影响。金属离子代谢：无镁条件下活化的CD8+T细胞代谢流和细胞因子释放较差。镁与LFA-1的两个亚基上的金属离子依赖的黏附部位结合，促进其活跃的“延伸”构象，从而使CD8+T细胞能够完全激活.锌内流在TCR信号转导和激活中也起着关键作用。TCR结扎后增加的锌内流减少了磷酸酶SHP1对TCR激活复合体的募集，并增加了ZAP70的磷酸化。代谢物钙离子同时还是TCR信号的特征之一，在TCR信号框架中是一个重要的离散信号。钙流是许多与T细胞激活相关的代谢变化的关键，可以诱导糖酵解和氧化磷酸化，并反过来受到代谢物的影响。不同的代谢产物对钙的流动有不同的调节作用，例如醋酸盐隔离钙流动，而维生素D促进钙流动。同一样代谢物的具体作用效果也受到细胞环境和暴露剂量的影响。例如，短链脂肪酸醋酸酯可以在TME中促进肿瘤浸润性淋巴细胞的效应功能，还能促进CD8+ T细胞的糖酵解，发挥免疫功能。但同时，暴露于高浓度的醋酸盐则会抑制钙离子流动，从而抑制CD8+ T细胞糖酵解。（二）代谢通过PI3K-AKT-mTOR通路调节共刺激信号。代谢物反馈并调节PI3K途径，PI3K途径激活会启动下游一系列信号，包括丝氨酸/苏氨酸激酶AKT的激活、NFAT核定位和mTOR激酶活性激活。每种代谢物则会向下游信号施加其独特的偏向，以影响T细胞的反应。PI3K-AKT糖酵解代谢过程在TCR激活后迅速上调促进PI3K活性，而磷脂酸和NAC促进AKT激活，从而进一步放大PI3K-AKT-mTOR信号通路。PI3K信号驱动维持强PI3K信号所需的代谢燃料的激活。甲氧丙戊酸代谢和丁酸则通过驱动mTORC1活性，提高T细胞初始激活时的翻译活性。维A酸(retinoic acid，RA)通过AKT信号和mTOR激活实现对CD4+ T细胞的激活作用。由于RA与RARα结合促进RARα的核定位，高浓度RA有利于RA介导的由核RARα介导的Treg细胞分化，而低浓度RA则通过T细胞代谢和Th17细胞介导的炎症反应促进高PI3K-AKT信号的表达。同时，LDHA缺乏的CD8+T细胞通过糖酵解产生的ATP减少，选择性地削弱PI3K依赖的信号，而使近端TCR信号不受影响。作为正反馈回路的一部分，AKT信号调节葡萄糖摄取。静息T细胞中AKT的结构性激活增加了葡萄糖摄取，但与CD28刺激的细胞中的葡萄糖摄取水平不匹配。磷脂酶D-1(PLD1)也促进T细胞激活过程中的AKT激活。mTORmTOR在PI3K-AKT信号下游被激活，但也受到许多代谢物的直接调节。鉴于mTOR是T细胞激活开始时的一个关键代谢开关，T细胞对外部来源代谢物对mTOR活性的调节高度敏感。因此，许多代谢物，包括氨基酸、脂肪酸和金属离子，都是改变T细胞代谢的离散信号。大多数改变T细胞命运的代谢物特异性信号很可能在mTOR途径内汇聚。氨基酸感应：在CD8+T细胞中，氨基酸缺乏会迅速削弱mTOR活性。缺乏ASCT2的CD4+T细胞对谷氨酰胺和亮氨酸的摄取减少，从而抑制mTORC1的激活，这可以通过摄入过量的谷氨酰胺或亮氨酸来弥补。氨基酸转运体LAT1介导细胞对组氨酸、苯丙氨酸和色氨酸等大的中性氨基酸的摄取，是维持CD8+T细胞mTORC1活性的关键。在肿瘤中，与细胞坏死相关的高水平的钾会削弱AKT-mTOR的磷酸化，并在体外和体内抑制CD8+T细胞的反应。钾通道Kv1.3在CD8+T细胞中的过表达增强了它们在肿瘤中的功能，并促进了B16黑色素瘤的清除。mTOR信号还受到脂质衍生的翻译后修饰以及丁酸盐等单链脂肪酸的可及性的影响。依赖Fntb的蛋白质预烯基化在Treg细胞激活期间维持mTORC1的活性。在翻译后修饰之外，用SCFA丁酸盐处理CD4+T细胞可促进mTOR激活。参考文献：1.Wilfahrt, D., Delgoffe, G.M. Metabolic waypoints during T cell differentiation. Nat Immunol (2024). https://doi.org/10.1038/s41590-023-01733-52.Ginefra, P., Hope, H. C., Spagna, M., Zecchillo, A. & Vannini, N. Ionic regulation of T-cell function and anti-tumour immunity. Int. J. Mol. Sci. 22, 13668 (2021).

2024-01-14

·生物谷

Nature子刊 | 范高峰和王皞鹏课题组揭示T细胞发育调控基因THEMIS作用机制

1月4日，上海科技大学生命科学与技术学院范高峰/王皞鹏课题组在Nature Structural & Molecular Biology上发表题为“THEMIS is a substrate and allosteric activator of SHP1, playing dual roles during T cell development”的研究论文，揭示T细胞发育调控基因THEMIS的具体作用机制，解决了该领域长期以来的争论。T细胞是获得性免疫系统中主要的功能执行者，负责识别抗原并做出免疫应答，而胸腺是T细胞发育和分化的场所。T细胞发育受到胸腺微环境和信号转导控制，这些过程在多个水平上受到精确的时空调控，其中酪氨酸磷酸化在T细胞信号级联中的调控尤为重要。为了揭示酪氨酸磷酸酶在T细胞中的底物谱图，本研究结合邻近标记技术PUP-IT和酪氨酸磷酸酶底物捕获突变体机制，开发了新技术PEPSI (PUP-IT Enhanced PTP Substrate Identification)用于高通量鉴定磷酸酶作用底物。研究人员通过PEPSI技术在T淋巴细胞中开展酪氨酸磷酸酶SHP1的底物鉴定，发现了SHP1的新型底物THEMIS，证实了THEMIS Y34位点的磷酸化修饰由LCK和SHP1进行正反调控。为揭示THEMIS磷酸化的生物学意义，本研究构建了THEMIS Y34F敲入和THEMIS敲除小鼠，通过流式细胞术分析小鼠T细胞发育和增殖情况，发现与THEMIS敲除小鼠的表型类似，THEMIS Y34F敲入小鼠胸腺T细胞从CD4和CD8双阳性阶段发育到CD4单阳性阶段有明显的阻滞，并且脾脏中的CD4单阳性T细胞明显减少。本研究还发现磷酸化的THEMIS可以激活SHP1，这提示THEMIS可能是SHP1的一个变构底物。进一步利用氢氘交换质谱、表面等离子共振等技术，发现磷酸化的THEMIS肽段结合SHP1的PTP结构域K520位点从而稳定SHP1的激活构象。图1. THEMIS Y34调控的CD4 T细胞发育本研究提出了新的THEMIS作用模型：在TCR刺激后，LCK磷酸化THEMIS的Y34位点，磷酸化的THEMIS将SHP1稳定在开放的构象，激活的SHP1会抑制TCR信号的传递，从而保证正常的阳性选择。该成果不仅揭示了调控T细胞发育的新机制和磷酸酶SHP1活性调控的新机制，并为研究TCR信号通路调控的机制和发掘潜在的T细胞治疗靶点提供了新思路。图2. THEMIS的作用模型上海科技大学生命学院常任副教授范高峰和常任副教授王皞鹏为论文的共同通讯作者，博士后张佳丽、博士研究生江振洲为论文的共同第一作者。上海科技大学生命学院常任正教授Tiffany Horng，常任副教授庄敏，助理教授张力烨，生命学院组学分析平台主任郝丕良，免疫化学所研究员白芳，中国农业科学院深圳农业基因组研究所研究员左二伟，中国科学院上海药物所研究员郑杰提供了大力支持。文章链接：https://www.nature.com/articles/s41594-023-01131-3本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！

细胞疗法