Weiguo Zhang
Adjunct Associate Professor in the Department of Immunology
Activation via the T-cell antigen receptor (TCR) triggers a cascade of intracellular biochemical events eventually leading to T-cell proliferation and effector functions. One of the earliest events is the activation of the Src family tyrosine kinases Fyn and Lck. The activated Src family kinases phosphorylate the CD3 subunits and TCRζ chains. ZAP-70 tyrosine kinase is recruited to the antigen receptors via the binding to CD3 and TCRζ. ZAP-70 is then tyrosine phosphorylated by these Src family kinases and thus activated. These activated tyrosine kinases further phosphorylate a number of intracellular proteins, such as PLC-γ1, Vav, Cbl, SLP-76, and LAT, and activate downstream signaling pathways including the Ras-MAPK pathway and Ca2+ flux. Activation of these two pathways is required for AP-1 and NFAT-mediated transcription, IL-2 production, and T-cell proliferation.
Our primary interest of the laboratory is to understand the role of membrane-associated adaptor proteins in lymphocyte activation, development, and immune response. One of these proteins is LAT (Linker for Activation of T-cells). LAT is tyrosine phosphorylated upon T-cell activation and associates with several signaling molecules including Grb2, Gads, and PLC-γ1. LAT-deficient T-cells are defective in the Ras-MAPK activation and Ca2+ flux after the TCR engagement. LAT knockout mice have an early block in thymocyte development. Interestingly, mice with a mutation in LAT develop a severe autoimmune disease. We are investigating how LAT interacts with other signaling proteins and how LAT regulates T cell activation and immune responses.
In addition to LAT, we are working on two LAT-like molecules, LAB and LAX. We have generated mice deficient in these proteins and are analyzing the phenotypes of these mice to determine the role of these proteins in lymphocyte signaling and immune responses.
We are also interested in FcεRI-mediated signaling. We are working on the role of LAT, LAB, and RasGRP1 in FcεRI-mediated signaling, mast cell function, and allergic responses.
Our long-term goal is to understand the details of immunoreceptor-mediated signaling pathways. Understanding these signaling pathways may identify therapeutic targets that could facilitate the development of drugs that suppress, modify, or augment immune responses in autoimmunity, transplantation, allergy, and cancer.
Current Appointments & Affiliations
- Adjunct Associate Professor in the Department of Immunology, Immunology, Basic Science Departments 2021
Contact Information
- 112 Jones Builidng, 207 Resear, Box 3010 DUMC, Durham, NC 27710
- Box 3010 DUMC, 112 Jones Building, Durham, NC 27710
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zhang033@mc.duke.edu
(919) 613-7803
- Background
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Education, Training, & Certifications
- Postdoctoral Fellow, Cell Biology And Metabolism Branch, National Institutes of Health 1995 - 1999
- Postdoctoral Fellow, Microbiology And Immunology, Yeshiva University New York 1994 - 1995
- Ph.D., Yeshiva University New York 1994
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Previous Appointments & Affiliations
- Member of the Duke Cancer Institute, Duke Cancer Institute, Institutes and Centers 1999 - 2021
- Associate Professor of Immunology, Immunology, Basic Science Departments 2006 - 2021
- Director of Undergraduate Studies, Immunology, Basic Science Departments 2012 - 2021
- Assistant Professor of Immunology, Immunology, Basic Science Departments 1999 - 2006
- Instructor, Temporary in the Department of Immunology, Immunology, Basic Science Departments 1999
- Publications & Artistic Works
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Selected Publications
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Academic Articles
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Liang, Ruonan, Shuaiyin Chen, Yuefei Jin, Ling Tao, Wangquan Ji, Peiyu Zhu, Dong Li, Yu Zhang, Weiguo Zhang, and Guangcai Duan. “The CXCL10/CXCR3 Axis Promotes Disease Pathogenesis in Mice upon CVA2 Infection.” Microbiol Spectr 10, no. 3 (June 29, 2022): e0230721. https://doi.org/10.1128/spectrum.02307-21.Full Text Link to Item
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Zhang, L., S. Chen, W. Zhang, H. Yang, Y. Jin, and G. Duan. “An Update on Animal Models for Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Countermeasure Development.” Frontiers in Microbiology 12 (November 8, 2021). https://doi.org/10.3389/fmicb.2021.770935.Full Text
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Zhang, Yu, Shuaiyin Chen, Yuefei Jin, Wangquan Ji, Weiguo Zhang, and Guangcai Duan. “An Update on Innate Immune Responses during SARS-CoV-2 Infection.” Viruses 13, no. 10 (October 2021): 2060. https://doi.org/10.3390/v13102060.Full Text
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Ji, Wangquan, Qiang Hu, Mengdi Zhang, Chuwen Zhang, Chen Chen, Yujie Yan, Xue Zhang, et al. “The Disruption of the Endothelial Barrier Contributes to Acute Lung Injury Induced by Coxsackievirus A2 Infection in Mice.” Int J Mol Sci 22, no. 18 (September 13, 2021). https://doi.org/10.3390/ijms22189895.Full Text Link to Item
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Ji, Wangquan, Peiyu Zhu, Ruonan Liang, Liang Zhang, Yu Zhang, Yuexia Wang, Weiguo Zhang, et al. “Coxsackievirus A2 Leads to Heart Injury in a Neonatal Mouse Model.” Viruses 13, no. 8 (August 11, 2021). https://doi.org/10.3390/v13081588.Full Text Link to Item
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Li, Dong, Shuaiyin Chen, Weiguo Zhang, Chao Zhang, Tiantian Sun, Yue Du, Ronghua Ding, Yanlei Gao, Yuefei Jin, and Guangcai Duan. “MicroRNA-628-5p Facilitates Enterovirus 71 Infection by Suppressing TRAF3 Signaling.” Cell Mol Immunol 18, no. 5 (May 2021): 1320–22. https://doi.org/10.1038/s41423-020-0453-4.Full Text Link to Item
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Zhao, Qiang, Yuntian Shen, Ran Li, Jiangbo Wu, Jingjun Lyu, Maorong Jiang, Liping Lu, et al. “Cardiac arrest and resuscitation activates the hypothalamic-pituitary-adrenal axis and results in severe immunosuppression.” J Cereb Blood Flow Metab 41, no. 5 (May 2021): 1091–1102. https://doi.org/10.1177/0271678X20948612.Full Text Open Access Copy Link to Item
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Jin, Yuefei, Tiantian Sun, Guangyuan Zhou, Dong Li, Shuaiyin Chen, Weiguo Zhang, Xueyuan Li, Rongguang Zhang, Haiyan Yang, and Guangcai Duan. “Pathogenesis Study of Enterovirus 71 Using a Novel Human SCARB2 Knock-In Mouse Model.” Msphere 6, no. 2 (March 10, 2021). https://doi.org/10.1128/mSphere.01048-20.Full Text Link to Item
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Zhu, Peiyu, Shuaiyin Chen, Weiguo Zhang, Guangcai Duan, and Yuefei Jin. “Essential Role of Non-Coding RNAs in Enterovirus Infection: From Basic Mechanisms to Clinical Prospects.” International Journal of Molecular Sciences 22, no. 6 (March 2021): 2904. https://doi.org/10.3390/ijms22062904.Full Text
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Ji, Wangquan, Luwei Qin, Ling Tao, Peiyu Zhu, Ruonan Liang, Guangyuan Zhou, Shuaiyin Chen, et al. “Neonatal Murine Model of Coxsackievirus A2 Infection for the Evaluation of Antiviral Therapeutics and Vaccination.” Frontiers in Microbiology 12 (January 2021): 658093. https://doi.org/10.3389/fmicb.2021.658093.Full Text
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Jin, Yuefei, Dong Li, Tiantian Sun, Yue Du, Yanlei Gao, Ronghua Ding, Wangquan Ji, et al. “Pathological Features of Enterovirus 71-Associated Brain and Lung Damage in Mice Based on Quantitative Proteomic Analysis.” Front Microbiol 12 (2021): 663019. https://doi.org/10.3389/fmicb.2021.663019.Full Text Link to Item
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O’Brien, Sarah A., Minghua Zhu, and Weiguo Zhang. “Spontaneous Differentiation of T Follicular Helper Cells in LATY136F Mutant Mice.” Frontiers in Immunology 12 (January 2021): 656817. https://doi.org/10.3389/fimmu.2021.656817.Full Text
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Jin, Yuefei, Wangquan Ji, Haiyan Yang, Shuaiyin Chen, Weiguo Zhang, and Guangcai Duan. “Endothelial activation and dysfunction in COVID-19: from basic mechanisms to potential therapeutic approaches.” Signal Transduct Target Ther 5, no. 1 (December 24, 2020): 293. https://doi.org/10.1038/s41392-020-00454-7.Full Text Link to Item
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Jiang, Maorong, Ran Li, Jingjun Lyu, Xuan Li, Wei Wang, Zhuoran Wang, Huaxin Sheng, Weiguo Zhang, Jörn Karhausen, and Wei Yang. “MCC950, a selective NLPR3 inflammasome inhibitor, improves neurologic function and survival after cardiac arrest and resuscitation.” Journal of Neuroinflammation 17, no. 1 (August 2020): 256. https://doi.org/10.1186/s12974-020-01933-y.Full Text Open Access Copy
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Chen, Shuaiyin, Xin Zheng, Jingyuan Zhu, Ronghua Ding, Yuefei Jin, Weiguo Zhang, HaiYan Yang, Yingjuan Zheng, Xin Li, and Guangcai Duan. “Extended ORF8 Gene Region Is Valuable in the Epidemiological Investigation of Severe Acute Respiratory Syndrome-Similar Coronavirus.” J Infect Dis 222, no. 2 (June 29, 2020): 223–33. https://doi.org/10.1093/infdis/jiaa278.Full Text Link to Item
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Jin, Yuefei, Haiyan Yang, Wangquan Ji, Weidong Wu, Shuaiyin Chen, Weiguo Zhang, and Guangcai Duan. “Virology, Epidemiology, Pathogenesis, and Control of COVID-19.” Viruses 12, no. 4 (March 27, 2020). https://doi.org/10.3390/v12040372.Full Text Link to Item
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Wu, Feihua, Yuan Chi, Zhonghao Jiang, Yuanyuan Xu, Ling Xie, Feifei Huang, Di Wan, et al. “Hydrogen peroxide sensor HPCA1 is an LRR receptor kinase in Arabidopsis.” Nature 578, no. 7796 (February 2020): 577–81. https://doi.org/10.1038/s41586-020-2032-3.Full Text Link to Item
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Lo, Wan-Lin, Neel H. Shah, Sara A. Rubin, Weiguo Zhang, Veronika Horkova, Ian R. Fallahee, Ondrej Stepanek, Leonard I. Zon, John Kuriyan, and Arthur Weiss. “Slow phosphorylation of a tyrosine residue in LAT optimizes T cell ligand discrimination.” Nat Immunol 20, no. 11 (November 2019): 1481–93. https://doi.org/10.1038/s41590-019-0502-2.Full Text Link to Item
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Jin, Yuefei, Minghua Zhu, Yanli Guo, Daniel Foreman, Feifei Feng, Guangcai Duan, Weidong Wu, and Weiguo Zhang. “Fine particulate matter (PM2.5) enhances FcεRI-mediated signaling and mast cell function.” Cellular Signalling 57 (May 2019): 102–9. https://doi.org/10.1016/j.cellsig.2019.01.010.Full Text
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Jin, Yuefei, Chao Zhang, Hui Wang, Guangyuan Zhou, Xiangpeng Wang, Rongguang Zhang, Shuaiyin Chen, et al. “Mast cells contribute to Enterovirus 71 infection-induced pulmonary edema in neonatal mice.” Lab Invest 98, no. 8 (August 2018): 1039–51. https://doi.org/10.1038/s41374-018-0075-y.Full Text Link to Item
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Zhu, Minghua, Daniel P. Foreman, Sarah A. O’Brien, Yuefei Jin, and Weiguo Zhang. “Phospholipase D in TCR-Mediated Signaling and T Cell Activation.” J Immunol 200, no. 6 (March 15, 2018): 2165–73. https://doi.org/10.4049/jimmunol.1701291.Full Text Link to Item
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Myers, Darienne R., Tannia Lau, Evan Markegard, Hyung W. Lim, Herbert Kasler, Minghua Zhu, Andrea Barczak, et al. “Tonic LAT-HDAC7 Signals Sustain Nur77 and Irf4 Expression to Tune Naive CD4 T Cells.” Cell Reports 19, no. 8 (May 2017): 1558–71. https://doi.org/10.1016/j.celrep.2017.04.076.Full Text
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Zhang, Baojun, Jianxuan Wu, Yiqun Jiao, Cheryl Bock, Meifang Dai, Benny Chen, Nelson Chao, Weiguo Zhang, and Yuan Zhuang. “Differential Requirements of TCR Signaling in Homeostatic Maintenance and Function of Dendritic Epidermal T Cells.” Journal of Immunology (Baltimore, Md. : 1950) 195, no. 9 (November 2015): 4282–91. https://doi.org/10.4049/jimmunol.1501220.Full Text
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Zhu, Minghua, Jianwei Zou, Tieshi Li, Sarah A. O’Brien, Yao Zhang, Sarah Ogden, and Weiguo Zhang. “Differential Roles of Phospholipase D Proteins in FcεRI-Mediated Signaling and Mast Cell Function.” J Immunol 195, no. 9 (November 1, 2015): 4492–4502. https://doi.org/10.4049/jimmunol.1500665.Full Text Link to Item
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O’Brien, Sarah A., Minghua Zhu, and Weiguo Zhang. “The Importance of IL-6 in the Development of LAT-Mediated Autoimmunity.” Journal of Immunology (Baltimore, Md. : 1950) 195, no. 2 (July 2015): 695–705. https://doi.org/10.4049/jimmunol.1403187.Full Text
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Wu, Xiaomei, Fei-Hua Wu, Xiaoqiang Wang, Lilin Wang, James N. Siedow, Weiguo Zhang, and Zhen-Ming Pei. “Molecular evolutionary and structural analysis of the cytosolic DNA sensor cGAS and STING.” Nucleic Acids Res 42, no. 13 (July 2014): 8243–57. https://doi.org/10.1093/nar/gku569.Full Text Link to Item
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Sullivan, Sarah A., Minghua Zhu, Steven Bao, Catherine A. Lewis, Chih-wen Ou-Yang, and Weiguo Zhang. “The role of LAT-PLCγ1 interaction in γδ T cell development and homeostasis.” Journal of Immunology (Baltimore, Md. : 1950) 192, no. 6 (March 2014): 2865–74. https://doi.org/10.4049/jimmunol.1302493.Full Text
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Suzuki, Ryo, Sarah Leach, Wenhua Liu, Evelyn Ralston, Jörg Scheffel, Weiguo Zhang, Clifford A. Lowell, and Juan Rivera. “Molecular editing of cellular responses by the high-affinity receptor for IgE.” Science 343, no. 6174 (February 28, 2014): 1021–25. https://doi.org/10.1126/science.1246976.Full Text Link to Item
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Suzuki, R., S. Leach, W. Liu, E. Ralston, J. Scheffel, W. Zhang, C. A. Lowell, and J. Rivera. “Molecular editing of cellular responses by the high-affinity receptor for IgE.” Science 343, no. 6174 (2014): 1021–25.
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Orr, Selinda J., Ashley R. Burg, Tim Chan, Laura Quigley, Gareth W. Jones, Jill W. Ford, Deborah Hodge, et al. “LAB/NTAL facilitates fungal/PAMP-induced IL-12 and IFN-γ production by repressing β-catenin activation in dendritic cells.” Plos Pathogens 9, no. 5 (May 2013): e1003357. https://doi.org/10.1371/journal.ppat.1003357.Full Text
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May, Rebecca M., Mariko Okumura, Chin-Jung Hsu, Hamid Bassiri, Enjun Yang, Gregory Rak, Emily M. Mace, et al. “Murine natural killer immunoreceptors use distinct proximal signaling complexes to direct cell function.” Blood 121, no. 16 (April 18, 2013): 3135–46. https://doi.org/10.1182/blood-2012-12-474361.Full Text Link to Item
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Ou-Yang, Chih-wen, Minghua Zhu, Sarah A. Sullivan, Deirdre M. Fuller, and Weiguo Zhang. “The requirement of linker for activation of T cells in the primary and memory responses of CD8 T cells.” J Immunol 190, no. 6 (March 15, 2013): 2938–47. https://doi.org/10.4049/jimmunol.1203163.Full Text Link to Item
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Fuller, Deirdre M., Minghua Zhu, Surapong Koonpaew, Mariana I. Nelson, and Weiguo Zhang. “The importance of the Erk pathway in the development of linker for activation of T cells-mediated autoimmunity.” Journal of Immunology (Baltimore, Md. : 1950) 189, no. 8 (October 2012): 4005–13. https://doi.org/10.4049/jimmunol.1201380.Full Text
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Chen, Yong, Xinxin Ci, Balachandra Gorentla, Sarah A. Sullivan, James C. Stone, Weiguo Zhang, Pablo Pereira, Jianxin Lu, and Xiao-Ping Zhong. “Differential requirement of RasGRP1 for γδ T cell development and activation.” Journal of Immunology (Baltimore, Md. : 1950) 189, no. 1 (July 2012): 61–71. https://doi.org/10.4049/jimmunol.1103272.Full Text
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Ou Yang, C. W., M. Zhu, D. M. Fuller, S. A. Sullivan, M. I. Chuck, S. Ogden, Q. J. Li, and W. Zhang. “Role of LAT in the granule-mediated cytotoxicity of CD8 T cells.” Molecular and Cellular Biology 32, no. 14 (July 2012): 2674–84. https://doi.org/10.1128/MCB.00356-12.Full Text
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Zhu, Minghua, Deirdre M. Fuller, and Weiguo Zhang. “The role of Ras guanine nucleotide releasing protein 4 in Fc epsilonRI-mediated signaling, mast cell function, and T cell development.” J Biol Chem 287, no. 11 (March 9, 2012): 8135–43. https://doi.org/10.1074/jbc.M111.320580.Full Text Link to Item
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Zhu, M., D. M. Fuller, C. W. Ou Yang, S. A. Sullivan, and W. Zhang. “Tyrosine phosphorylation-independent regulation of lipopolysaccharide-mediated response by the transmembrane adaptor protein LAB.” Journal of Immunology 188, no. 6 (March 2012): 2733–41. https://doi.org/10.4049/jimmunol.1101581.Full Text
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Fuller, Deirdre M., Minghua Zhu, Xiaohua Song, Chih-wen Ou-Yang, Sarah A. Sullivan, James C. Stone, and Weiguo Zhang. “Regulation of RasGRP1 function in T cell development and activation by its unique tail domain.” Plos One 7, no. 6 (2012): e38796. https://doi.org/10.1371/journal.pone.0038796.Full Text Link to Item
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Fuller, D. M., M. Zhu, C. W. Ou Yang, S. A. Sullivan, and W. Zhang. “A tale of two TRAPs: LAT and LAB in the regulation of lymphocyte development, activation, and autoimmunity.” Immunologic Research 49, no. 1–3 (April 2011): 97–108. https://doi.org/10.1007/s12026-010-8197-3.Full Text
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Markegard, Evan, Evan Trager, Chih-wen Ou Yang, Weiguo Zhang, Arthur Weiss, and Jeroen P. Roose. “Basal LAT-diacylglycerol-RasGRP1 signals in T cells maintain TCRα gene expression.” Plos One 6, no. 9 (January 2011): e25540. https://doi.org/10.1371/journal.pone.0025540.Full Text
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Shen, Shudan, Mariana I. Chuck, Minghua Zhu, Deirdre M. Fuller, Chih-Wen Ou Yang, and Weiguo Zhang. “The importance of LAT in the activation, homeostasis, and regulatory function of T cells.” J Biol Chem 285, no. 46 (November 12, 2010): 35393–405. https://doi.org/10.1074/jbc.M110.145052.Full Text Link to Item
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Kambayashi, T., M. Okumura, R. G. Baker, C. J. Hsu, T. Baumgart, W. Zhang, and G. A. Koretzky. “Independent and cooperative roles of adaptor molecules in proximal signaling during FcepsilonRI-mediated mast cell activation.” Molecular and Cellular Biology 30, no. 17 (September 2010): 4188–96. https://doi.org/10.1128/MCB.00305-10.Full Text
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Chuck, Mariana I., Minghua Zhu, Shudan Shen, and Weiguo Zhang. “The role of the LAT-PLC-gamma1 interaction in T regulatory cell function.” Journal of Immunology (Baltimore, Md. : 1950) 184, no. 5 (March 2010): 2476–86. https://doi.org/10.4049/jimmunol.0902876.Full Text
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Whittaker, Gillian C., Selinda J. Orr, Laura Quigley, Laurel Hughes, Ivo M. B. Francischetti, Weigou Zhang, and Daniel W. McVicar. “The linker for activation of B cells (LAB)/non-T cell activation linker (NTAL) regulates triggering receptor expressed on myeloid cells (TREM)-2 signaling and macrophage inflammatory responses independently of the linker for activation of T cells.” J Biol Chem 285, no. 5 (January 29, 2010): 2976–85. https://doi.org/10.1074/jbc.M109.038398.Full Text Link to Item
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Malhotra, Shikha, Susan Kovats, Weiguo Zhang, and K Mark Coggeshall. “Vav and Rac activation in B cell antigen receptor endocytosis involves Vav recruitment to the adapter protein LAB.” J Biol Chem 284, no. 52 (December 25, 2009): 36202–12. https://doi.org/10.1074/jbc.M109.040089.Full Text Link to Item
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Fuller, Deirdre M., and Weiguo Zhang. “Regulation of lymphocyte development and activation by the LAT family of adapter proteins.” Immunol Rev 232, no. 1 (November 2009): 72–83. https://doi.org/10.1111/j.1600-065X.2009.00828.x.Full Text Link to Item
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Malhotra, Shikha, Susan Kovats, Weiguo Zhang, and K Mark Coggeshall. “B cell antigen receptor endocytosis and antigen presentation to T cells require Vav and dynamin.” J Biol Chem 284, no. 36 (September 4, 2009): 24088–97. https://doi.org/10.1074/jbc.M109.014209.Full Text Link to Item
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Hundt, M., Y. Harada, L. De Giorgio, N. Tanimura, W. Zhang, and A. Altman. “Palmitoylation-dependent plasma membrane transport but lipid raft-independent signaling by linker for activation of T cells.” Journal of Immunology 183, no. 3 (August 2009): 1685–94. https://doi.org/10.4049/jimmunol.0803921.Full Text
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Shen, S., J. Lau, M. Zhu, J. Zou, D. Fuller, Q. J. Li, and W. Zhang. “The importance of Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons sterile-alpha motif domain in thymic selection and T-cell activation.” Blood 114, no. 1 (July 2009): 74–84.
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Shen, Shudan, Minghua Zhu, Jasmine Lau, Mariana Chuck, and Weiguo Zhang. “The essential role of LAT in thymocyte development during transition from the double-positive to single-positive stage.” Journal of Immunology (Baltimore, Md. : 1950) 182, no. 9 (May 2009): 5596–5604. https://doi.org/10.4049/jimmunol.0803170.Full Text
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Shapiro, M. J., C. T. Nguyen, H. Aghajanian, W. Zhang, and V. S. Shapiro. “Negative regulation of TCR signaling by linker for activation of X cells via phosphotyrosine-dependent and -independent mechanisms.” Journal of Immunology 181, no. 10 (November 2008): 7055–61.
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Liu, Yan, and Weiguo Zhang. “Identification of a new transmembrane adaptor protein that constitutively binds Grb2 in B cells.” J Leukoc Biol 84, no. 3 (September 2008): 842–51. https://doi.org/10.1189/jlb.0208087.Full Text Link to Item
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Whittaker, G. C., D. N. Burshtyn, S. J. Orr, L. Quigley, D. L. Hodge, V. Pascal, W. Zhang, and D. W. McVicar. “Analysis of the linker for activation of T cells (LAT) and the linker for activation of B cells (LAB) in natural killer cells reveals a novel signaling cassette, dual usage in ITAM signaling, and influence on development of the Ly49 repertoire.” Blood, July 2008.
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Hundt, Matthias, Yoshuke Harada, Keitaro Hayashi, Lauren De Giorgio, Natsuko Tanimura, Weiguo Zhang, and Amnon Altman. “Palmitoylation-dependent plasma membrane transport, but lipid raft-independent signaling function, of linker for activation of T cells (LAT).” Faseb Journal 22 (2008).Link to Item
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Denning, T. L., S. Granger, D. Mucida, R. Graddy, G. Leclercq, W. Zhang, K. Honey, et al. “Erratum: Mouse TCRαβ+CD8αα intraepithelial lymphocytes express genes that down-regulate their antigen reactivity and suppress immune responses (Journal of Immunology (2007) 178, (4230-4239)).” Journal of Immunology 178, no. 10 (May 15, 2007): 6654.
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Denning, Timothy L., Steve W. Granger, Daniel Mucida, Ryan Graddy, Georges Leclercq, Weiguo Zhang, Karen Honey, et al. “Mouse TCRalphabeta+CD8alphaalpha intraepithelial lymphocytes express genes that down-regulate their antigen reactivity and suppress immune responses.” J Immunol 178, no. 7 (April 1, 2007): 4230–39. https://doi.org/10.4049/jimmunol.178.7.4230.Full Text Link to Item
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Liu, Yan, Minghua Zhu, Keigo Nishida, Toshio Hirano, and Weiguo Zhang. “An essential role for RasGRP1 in mast cell function and IgE-mediated allergic response.” J Exp Med 204, no. 1 (January 22, 2007): 93–103. https://doi.org/10.1084/jem.20061598.Full Text Link to Item
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Mutch, C. M., R. Sanyal, T. L. Unruh, L. Grigoriou, M. Zhu, W. Zhang, and J. P. Deans. “Activation-induced endocytosis of the raft-associated transmembrane adaptor protein LAB/NTAL in B lymphocytes: evidence for a role in internalization of the B cell receptor.” International Immunology 19, no. 1 (January 2007): 19–30.
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Zhu, M., S. Koonpaew, Y. Liu, S. Shen, T. Denning, I. Dzhagalov, I. Rhee, and W. Zhang. “Negative regulation of T cell activation and autoimmunity by the transmembrane adaptor protein LAB.” Immunity 25, no. 5 (November 2006): 757–68.
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Zhu, Minghua, Inmoo Rhee, Yan Liu, and Weiguo Zhang. “Negative regulation of Fc epsilonRI-mediated signaling and mast cell function by the adaptor protein LAX.” J Biol Chem 281, no. 27 (July 7, 2006): 18408–13. https://doi.org/10.1074/jbc.M601535200.Full Text Link to Item
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Koonpaew, Surapong, Shudan Shen, Lawrence Flowers, and Weiguo Zhang. “LAT-mediated signaling in CD4+CD25+ regulatory T cell development.” The Journal of Experimental Medicine 203, no. 1 (January 2006): 119–29. https://doi.org/10.1084/jem.20050903.Full Text
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Zhu, Minghua, Olivia Granillo, Renren Wen, Kaiyong Yang, Xuezhi Dai, Demin Wang, and Weiguo Zhang. “Negative regulation of lymphocyte activation by the adaptor protein LAX.” J Immunol 174, no. 9 (May 1, 2005): 5612–19. https://doi.org/10.4049/jimmunol.174.9.5612.Full Text Link to Item
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Zhu, M., S. Shen, Y. Liu, O. Granillo, and W. Zhang. “Cutting Edge: Localization of linker for activation of T cells to lipid rafts is not essential in T cell activation and development.” Journal of Immunology 174, no. 1 (January 2005): 31–35.
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Wen, R., Y. Chen, J. Schuman, G. Fu, S. Yang, W. Zhang, D. K. Newman, and D. Wang. “An important role of phospholipase Cgamma1 in pre-B-cell development and allelic exclusion.” The Embo Journal 23, no. 20 (October 2004): 4007–17.
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Zhu, M., Y. Liu, S. Koonpaew, O. Granillo, and W. Zhang. “Positive and negative regulation of FcepsilonRI-mediated signaling by the adaptor protein LAB/NTAL.” The Journal of Experimental Medicine 200, no. 8 (October 2004): 991–1000.
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Horejsí, Václav, Weiguo Zhang, and Burkhart Schraven. “Transmembrane adaptor proteins: organizers of immunoreceptor signalling.” Nat Rev Immunol 4, no. 8 (August 2004): 603–16. https://doi.org/10.1038/nri1414.Full Text Link to Item
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Zipfel, Patricia A., Weiguo Zhang, Marisol Quiroz, and Ann Marie Pendergast. “Requirement for Abl kinases in T cell receptor signaling.” Current Biology : Cb 14, no. 14 (July 2004): 1222–31. https://doi.org/10.1016/j.cub.2004.07.021.Full Text
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Janssen, Erin, Minghua Zhu, Brandon Craven, and Weiguo Zhang. “Linker for activation of B cells: a functional equivalent of a mutant linker for activation of T cells deficient in phospholipase C-gamma1 binding.” Journal of Immunology (Baltimore, Md. : 1950) 172, no. 11 (June 2004): 6810–19. https://doi.org/10.4049/jimmunol.172.11.6810.Full Text
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Koonpaew, Surapong, Erin Janssen, Minghua Zhu, and Weiguo Zhang. “The importance of three membrane-distal tyrosines in the adaptor protein NTAL/LAB.” The Journal of Biological Chemistry 279, no. 12 (March 2004): 11229–35. https://doi.org/10.1074/jbc.m311394200.Full Text
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Hořejší, V., W. Zhang, and B. Schraven. “Erratum: Transmembrane adaptor proteins: Organizers of immunoreceptor signalling (Nature Reviews Immunology (2004) 4 (603-616)).” Nature Reviews Immunology 4, no. 9 (January 1, 2004): 743. https://doi.org/10.1038/nri1455.Full Text
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Janssen, Erin, and Weiguo Zhang. “Adaptor proteins in lymphocyte activation.” Current Opinion in Immunology 15, no. 3 (June 2003): 269–76. https://doi.org/10.1016/s0952-7915(03)00044-x.Full Text
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Janssen, Erin, Minghua Zhu, Weijia Zhang, Surapong Koonpaew, and Weiguo Zhang. “LAB: a new membrane-associated adaptor molecule in B cell activation.” Nat Immunol 4, no. 2 (February 2003): 117–23. https://doi.org/10.1038/ni882.Full Text Link to Item
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Zhu, Minghua, Erin Janssen, and Weiguo Zhang. “Minimal requirement of tyrosine residues of linker for activation of T cells in TCR signaling and thymocyte development.” J Immunol 170, no. 1 (January 1, 2003): 325–33. https://doi.org/10.4049/jimmunol.170.1.325.Full Text Link to Item
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Zhu, Minghua, Erin Janssen, Kin Leung, and Weiguo Zhang. “Molecular cloning of a novel gene encoding a membrane-associated adaptor protein (LAX) in lymphocyte signaling.” J Biol Chem 277, no. 48 (November 29, 2002): 46151–58. https://doi.org/10.1074/jbc.M208946200.Full Text Link to Item
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Sommers, C. L., R. K. Menon, A. Grinberg, W. Zhang, L. E. Samelson, and P. E. Love. “Knock-in mutation of the distal four tyrosines of linker for activation of T cells blocks murine T cell development.” J Exp Med 194, no. 2 (July 16, 2001): 135–42. https://doi.org/10.1084/jem.194.2.135.Full Text Link to Item
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Bunnell, S. C., V. Kapoor, R. P. Trible, W. Zhang, and L. E. Samelson. “Dynamic actin polymerization drives T cell receptor-induced spreading: a role for the signal transduction adaptor LAT.” Immunity 14, no. 3 (March 2001): 315–29. https://doi.org/10.1016/s1074-7613(01)00112-1.Full Text Link to Item
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Martelli, M. P., H. Lin, W. Zhang, L. E. Samelson, and B. E. Bierer. “Signaling via LAT (linker for T-cell activation) and Syk/ZAP70 is required for ERK activation and NFAT transcriptional activation following CD2 stimulation.” Blood 96, no. 6 (September 15, 2000): 2181–90.Link to Item
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Zhang, W., R. P. Trible, M. Zhu, S. K. Liu, C. J. McGlade, and L. E. Samelson. “Association of Grb2, Gads, and phospholipase C-gamma 1 with phosphorylated LAT tyrosine residues. Effect of LAT tyrosine mutations on T cell angigen receptor-mediated signaling.” J Biol Chem 275, no. 30 (July 28, 2000): 23355–61. https://doi.org/10.1074/jbc.M000404200.Full Text Link to Item
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Saitoh, S., R. Arudchandran, T. S. Manetz, W. Zhang, C. L. Sommers, P. E. Love, J. Rivera, and L. E. Samelson. “LAT is essential for Fc(epsilon)RI-mediated mast cell activation.” Immunity 12, no. 5 (May 2000): 525–35. https://doi.org/10.1016/s1074-7613(00)80204-6.Full Text
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Zhang, W., and L. E. Samelson. “The role of membrane-associated adaptors in T cell receptor signalling.” Seminars in Immunology 12, no. 1 (February 2000): 35–41.
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Pasquet, J. M., B. Gross, L. Quek, N. Asazuma, W. Zhang, C. L. Sommers, E. Schweighoffer, et al. “LAT is required for tyrosine phosphorylation of phospholipase cgamma2 and platelet activation by the collagen receptor GPVI.” Mol Cell Biol 19, no. 12 (December 1999): 8326–34. https://doi.org/10.1128/MCB.19.12.8326.Full Text Link to Item
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Bosselut, R., W. Zhang, J. M. Ashe, J. L. Kopacz, L. E. Samelson, and A. Singer. “Association of the adaptor molecule LAT with CD4 and CD8 coreceptors identifies a new coreceptor function in T cell receptor signal transduction.” The Journal of Experimental Medicine 190, no. 10 (November 1999): 1517–26. https://doi.org/10.1084/jem.190.10.1517.Full Text
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Lindholm, C. K., E. Gylfe, W. Zhang, L. E. Samelson, and M. Welsh. “Requirement of the Src homology 2 domain protein Shb for T cell receptor-dependent activation of the interleukin-2 gene nuclear factor for activation of T cells element in Jurkat T cells.” J Biol Chem 274, no. 39 (September 24, 1999): 28050–57. https://doi.org/10.1074/jbc.274.39.28050.Full Text Link to Item
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Zhang, W., B. J. Irvin, R. P. Trible, R. T. Abraham, and L. E. Samelson. “Functional analysis of LAT in TCR-mediated signaling pathways using a LAT-deficient Jurkat cell line.” Int Immunol 11, no. 6 (June 1999): 943–50. https://doi.org/10.1093/intimm/11.6.943.Full Text Link to Item
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Facchetti, F., J. K. Chan, W. Zhang, A. Tironi, M. Chilosi, S. Parolini, L. D. Notarangelo, and L. E. Samelson. “Linker for activation of T cells (LAT), a novel immunohistochemical marker for T cells, NK cells, mast cells, and megakaryocytes: evaluation in normal and pathological conditions.” The American Journal of Pathology 154, no. 4 (April 1999): 1037–46. https://doi.org/10.1016/s0002-9440(10)65356-4.Full Text
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Jevremovic, D., D. D. Billadeau, R. A. Schoon, C. J. Dick, B. J. Irvin, W. Zhang, L. E. Samelson, R. T. Abraham, and P. J. Leibson. “Cutting edge: a role for the adaptor protein LAT in human NK cell-mediated cytotoxicity.” J Immunol 162, no. 5 (March 1, 1999): 2453–56.Link to Item
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Zhang, W., C. L. Sommers, D. N. Burshtyn, C. C. Stebbins, J. B. DeJarnette, R. P. Trible, A. Grinberg, et al. “Essential role of LAT in T cell development.” Immunity 10, no. 3 (March 1999): 323–32. https://doi.org/10.1016/s1074-7613(00)80032-1.Full Text Link to Item
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Samelson, L. E., S. C. Bunnell, R. P. Trible, T. Yamazaki, and W. Zhang. “Studies on the adapter molecule LAT.” Cold Spring Harbor Symposia on Quantitative Biology 64 (January 1999): 259–63. https://doi.org/10.1101/sqb.1999.64.259.Full Text
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Lee, K. M., E. Chuang, M. Griffin, R. Khattri, D. K. Hong, W. Zhang, D. Straus, L. E. Samelson, C. B. Thompson, and J. A. Bluestone. “Molecular basis of T cell inactivation by CTLA-4.” Science 282, no. 5397 (December 18, 1998): 2263–66. https://doi.org/10.1126/science.282.5397.2263.Full Text Link to Item
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Finco, T. S., T. Kadlecek, W. Zhang, L. E. Samelson, and A. Weiss. “LAT is required for TCR-mediated activation of PLCgamma1 and the Ras pathway.” Immunity 9, no. 5 (November 1998): 617–26. https://doi.org/10.1016/s1074-7613(00)80659-7.Full Text Link to Item
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Zhang, W., R. P. Trible, and L. E. Samelson. “LAT palmitoylation: its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation.” Immunity 9, no. 2 (August 1998): 239–46. https://doi.org/10.1016/s1074-7613(00)80606-8.Full Text Link to Item
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Griffith, C. E., W. Zhang, and R. L. Wange. “ZAP-70-dependent and -independent activation of Erk in Jurkat T cells. Differences in signaling induced by H2o2 and Cd3 cross-linking.” J Biol Chem 273, no. 17 (April 24, 1998): 10771–76. https://doi.org/10.1074/jbc.273.17.10771.Full Text Link to Item
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Williams, B. L., K. L. Schreiber, W. Zhang, R. L. Wange, L. E. Samelson, P. J. Leibson, and R. T. Abraham. “Genetic evidence for differential coupling of Syk family kinases to the T-cell receptor: reconstitution studies in a ZAP-70-deficient Jurkat T-cell line.” Mol Cell Biol 18, no. 3 (March 1998): 1388–99. https://doi.org/10.1128/MCB.18.3.1388.Full Text Link to Item
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Zhang, W., J. Sloan-Lancaster, J. Kitchen, R. P. Trible, and L. E. Samelson. “LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation.” Cell 92, no. 1 (January 9, 1998): 83–92. https://doi.org/10.1016/s0092-8674(00)80901-0.Full Text Link to Item
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Sloan-Lancaster, J., W. Zhang, J. Presley, B. L. Williams, R. T. Abraham, J. Lippincott-Schwartz, and L. E. Samelson. “Regulation of ZAP-70 intracellular localization: visualization with the green fluorescent protein.” The Journal of Experimental Medicine 186, no. 10 (November 1997): 1713–24. https://doi.org/10.1084/jem.186.10.1713.Full Text
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Eischen, C. M., B. L. Williams, W. Zhang, L. E. Samelson, D. H. Lynch, R. T. Abraham, and P. J. Leibson. “ZAP-70 tyrosine kinase is required for the up-regulation of Fas ligand in activation-induced T cell apoptosis.” Journal of Immunology (Baltimore, Md. : 1950) 159, no. 3 (August 1997): 1135–39.
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Young, A. C., W. Zhang, J. C. Sacchettini, and S. G. Nathenson. “MHC class I-peptide interactions and TCR recognition.” Cancer Surv 22 (1995): 17–36.Link to Item
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Young, A. C., W. Zhang, J. C. Sacchettini, and S. G. Nathenson. “The three-dimensional structure of H-2Db at 2.4 A resolution: implications for antigen-determinant selection.” Cell 76, no. 1 (January 14, 1994): 39–50. https://doi.org/10.1016/0092-8674(94)90171-6.Full Text Link to Item
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Zhang, W., A. C. Young, M. Imarai, S. G. Nathenson, and J. C. Sacchettini. “Crystal structure of the major histocompatibility complex class I H-2Kb molecule containing a single viral peptide: implications for peptide binding and T-cell receptor recognition.” Proc Natl Acad Sci U S A 89, no. 17 (September 1, 1992): 8403–7. https://doi.org/10.1073/pnas.89.17.8403.Full Text Link to Item
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Nathenson, S. G., G. M. Van Bleek, J. Geliebter, K. Hasenkrug, M. Imarai, S. Joyce, K. Kesari, et al. “Specificity of interaction between MHC (major histocompatibility complex) class I molecules, antigenic peptides, and the T cell receptor.” Developmental and Comparative Immunology 15, no. SUPPL. 1 (January 1, 1991). https://doi.org/10.1016/0145-305X(91)90201-9.Full Text
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Conference Papers
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Zhang, Baojun, Cheryl Bock, Jianxuan Wu, Yiqun Jiao, Benny Chen, Nelson Chao, Weiguo Zhang, and Yuan Zhuang. “LAT-mediated TCR signaling is required for optimal function and clonal expansion but not long-term survival and homeostatic turnover of DETCs.” In Journal of Immunology, Vol. 194. AMER ASSOC IMMUNOLOGISTS, 2015.Link to Item
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Zhang, Weiguo, Sarah Sullivan, Minghua Zhu, and Catherine Lewis. “Linker for activation of T cells (LAT) in the regulation of T cell activation and autoimmunity.” In Journal of Immunology, Vol. 192. AMER ASSOC IMMUNOLOGISTS, 2014.Link to Item
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Fuller, Deirdre, and Weiguo Zhang. “Regulation of Erk activation in T cells through the tail domain of RasGRP1.” In Journal of Immunology, Vol. 186. AMER ASSOC IMMUNOLOGISTS, 2011.Link to Item
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Ouyang, Chihwen Claudia, Minghua Zhu, Qi-jing Li, and Weiguo Zhang. “LAT-independent triggering of granule-mediated cytotoxicity of CD8 T cells.” In Journal of Immunology, Vol. 186. AMER ASSOC IMMUNOLOGISTS, 2011.Link to Item
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Orr, Selinda, Laura Quigley, Stephen Roessler, Deborah Hodge, Catherine Razzook, Marco Cardone, Weiguo Zhang, Giorgio Trinchieri, Lyudmila Lyakh, and Daniel McVicar. “LAB/NTAL regulates zymosan-mediated inflammatory responses in Bone Marrow Derived Dendritic Cells (BMDC).” In Journal of Immunology, Vol. 184. AMER ASSOC IMMUNOLOGISTS, 2010.Link to Item
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Shen, Shudan, Minghua Zhu, and Weiguo Zhang. “LAT Plays Important Role in Thymocyte Survival and Mature T Cell Activation.” In Journal of Immunology, Vol. 178. AMER ASSOC IMMUNOLOGISTS, 2007.Link to Item
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