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Weiguo Zhang

Adjunct Associate Professor in the Department of Immunology
Integrative Immunobiology
Box 3010 DUMC, 112 Jones Building, Durham, NC 27710
112 Jones Builidng, 207 Resear, Box 3010 DUMC, Durham, NC 27710

Selected Publications


Local immune dysregulation and subsequent inflammatory response contribute to pulmonary edema caused by Enterovirus infection in mice.

Journal Article J Med Virol · February 2023 Pulmonary edema that comes on suddenly is the leading cause of mortality in hand-foot-and-mouth disease (HFMD) patients; however, its pathogenesis is still largely unclear. A range of research suggest immunopathogenesis during the occurrence of pulmonary e ... Full text Link to item Cite

The CXCL10/CXCR3 Axis Promotes Disease Pathogenesis in Mice upon CVA2 Infection.

Journal Article Microbiol Spectr · June 29, 2022 Coxsackievirus A2 (CVA2) is an emerging pathogen that results in hand-foot-and-mouth disease (HFMD) outbreaks. Systemic inflammatory response and central nervous system inflammation are the main pathological features of fatal HFMD. However, the immunopatho ... Full text Link to item Cite

An Update on Animal Models for Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Countermeasure Development

Journal Article Frontiers in Microbiology · November 8, 2021 Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic since March 2020 and led to significant challenges to over 200 countries and regions all over the world. The establishment of h ... Full text Cite

An Update on Innate Immune Responses during SARS-CoV-2 Infection.

Journal Article Viruses · October 14, 2021 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the Coronaviridae family, which is responsible for the COVID-19 pandemic followed by unprecedented global societal and economic disruptive impact. The innate immune system is t ... Full text Link to item Cite

The Disruption of the Endothelial Barrier Contributes to Acute Lung Injury Induced by Coxsackievirus A2 Infection in Mice.

Journal Article Int J Mol Sci · September 13, 2021 Sporadic occurrences and outbreaks of hand, foot, and mouth disease (HFMD) caused by Coxsackievirus A2 (CVA2) have frequently reported worldwide recently, which pose a great challenge to public health. Epidemiological studies have suggested that the main c ... Full text Link to item Cite

Coxsackievirus A2 Leads to Heart Injury in a Neonatal Mouse Model.

Journal Article Viruses · August 11, 2021 Coxsackievirus A2 (CVA2) has emerged as an active pathogen that has been implicated in hand, foot, and mouth disease (HFMD) and herpangina outbreaks worldwide. It has been reported that severe cases with CVA2 infection develop into heart injury, which may ... Full text Link to item Cite

Cardiac arrest and resuscitation activates the hypothalamic-pituitary-adrenal axis and results in severe immunosuppression.

Journal Article J Cereb Blood Flow Metab · May 2021 In patients who are successfully resuscitated after initial cardiac arrest (CA), mortality and morbidity rates are high, due to ischemia/reperfusion injury to the whole body including the nervous and immune systems. How the interactions between these two c ... Full text Open Access Link to item Cite

Essential Role of Non-Coding RNAs in Enterovirus Infection: From Basic Mechanisms to Clinical Prospects.

Journal Article Int J Mol Sci · March 12, 2021 Enteroviruses (EVs) are common RNA viruses that can cause various types of human diseases and conditions such as hand, foot, and mouth disease (HFMD), myocarditis, meningitis, sepsis, and respiratory disorders. Although EV infections in most patients are g ... Full text Link to item Cite

Pathogenesis Study of Enterovirus 71 Using a Novel Human SCARB2 Knock-In Mouse Model.

Journal Article mSphere · March 10, 2021 Enterovirus 71 (EV71) can cause a severe hand-foot-mouth disease in children. However, the precise mechanism of EV71-associated disease, particularly the neuropathogenesis and pulmonary disorder, is still not fully understood because no suitable animal mod ... Full text Link to item Cite

Spontaneous Differentiation of T Follicular Helper Cells in LATY136F Mutant Mice.

Journal Article Front Immunol · 2021 Mice with a mutation at the LAT-PLCγ1 binding site (Y136) have a defect in thymocyte development due to dampened TCR signaling. CD4+ T cells that do reach the periphery are hyper-activated and skewed to Th2. Over time, these mice develop an autoimmune-like ... Full text Link to item Cite

Neonatal Murine Model of Coxsackievirus A2 Infection for the Evaluation of Antiviral Therapeutics and Vaccination.

Journal Article Front Microbiol · 2021 Coxsackievirus (CV) A2 has emerged as an important etiological agent in the pathogen spectrum of hand, foot, and mouth disease (HFMD). The symptoms of CVA2 infections are generally mild, but worsen rapidly in some people, posing a serious threat to childre ... Full text Link to item Cite

Pathological Features of Enterovirus 71-Associated Brain and Lung Damage in Mice Based on Quantitative Proteomic Analysis.

Journal Article Front Microbiol · 2021 The outbreaks of enterovirus 71 (EV71)-associated hand, foot, and mouth disease (HFMD) have emerged as an emergency of global health due to its association with fatal encephalitis and subsequent neurogenic pulmonary edema; however, the molecular characteri ... Full text Link to item Cite

Endothelial activation and dysfunction in COVID-19: from basic mechanisms to potential therapeutic approaches.

Journal Article Signal Transduct Target Ther · December 24, 2020 On 12 March 2020, the outbreak of coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization. As of 4 August 2020, more than 18 million confirmed infections had been reported globally. Most patients have mild symptoms, but ... Full text Link to item Cite

MCC950, a selective NLPR3 inflammasome inhibitor, improves neurologic function and survival after cardiac arrest and resuscitation.

Journal Article J Neuroinflammation · August 31, 2020 BACKGROUND: Cardiac arrest (CA) is associated with high morbidity and mortality, even after spontaneous circulation is re-established. This dire situation is partly due to post-CA syndrome for which no specific and effective intervention is available. One ... Full text Open Access Link to item Cite

Extended ORF8 Gene Region Is Valuable in the Epidemiological Investigation of Severe Acute Respiratory Syndrome-Similar Coronavirus.

Journal Article J Infect Dis · June 29, 2020 Severe acute respiratory syndrome coronavirus (SARS-CoV) was discovered as a novel pathogen in the 2002-2003 SARS epidemic. The emergence and disappearance of this pathogen have brought questions regarding its source and evolution. Within the genome sequen ... Full text Link to item Cite

Virology, Epidemiology, Pathogenesis, and Control of COVID-19.

Journal Article Viruses · March 27, 2020 The outbreak of emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) in China has been brought to global attention and declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Scientific advancements ... Full text Link to item Cite

Hydrogen peroxide sensor HPCA1 is an LRR receptor kinase in Arabidopsis.

Journal Article Nature · February 2020 Featured Publication Hydrogen peroxide (H2O2) is a major reactive oxygen species in unicellular and multicellular organisms, and is produced extracellularly in response to external stresses and internal cues1-4. H2O2 enters cells through aquaporin membrane proteins and covalen ... Full text Link to item Cite

Slow phosphorylation of a tyrosine residue in LAT optimizes T cell ligand discrimination.

Journal Article Nat Immunol · November 2019 Featured Publication Self-non-self discrimination is central to T cell-mediated immunity. The kinetic proofreading model can explain T cell antigen receptor (TCR) ligand discrimination; however, the rate-limiting steps have not been identified. Here, we show that tyrosine phos ... Full text Link to item Cite

Fine particulate matter (PM2.5) enhances FcεRI-mediated signaling and mast cell function.

Journal Article Cell Signal · May 2019 Persistent exposure to ambient fine particulate matter (PM2.5) can exacerbate allergic diseases in humans. Mast cells play an important role in allergic inflammation in peripheral tissues, such as skin, mucosa, and lung. Engagement of the high-affinity Fc ... Full text Link to item Cite

Local immune dysregulation and subsequent inflammatory response contribute to pulmonary edema caused by Enterovirus infection in mice.

Journal Article J Med Virol · February 2023 Pulmonary edema that comes on suddenly is the leading cause of mortality in hand-foot-and-mouth disease (HFMD) patients; however, its pathogenesis is still largely unclear. A range of research suggest immunopathogenesis during the occurrence of pulmonary e ... Full text Link to item Cite

The CXCL10/CXCR3 Axis Promotes Disease Pathogenesis in Mice upon CVA2 Infection.

Journal Article Microbiol Spectr · June 29, 2022 Coxsackievirus A2 (CVA2) is an emerging pathogen that results in hand-foot-and-mouth disease (HFMD) outbreaks. Systemic inflammatory response and central nervous system inflammation are the main pathological features of fatal HFMD. However, the immunopatho ... Full text Link to item Cite

An Update on Animal Models for Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Countermeasure Development

Journal Article Frontiers in Microbiology · November 8, 2021 Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic since March 2020 and led to significant challenges to over 200 countries and regions all over the world. The establishment of h ... Full text Cite

An Update on Innate Immune Responses during SARS-CoV-2 Infection.

Journal Article Viruses · October 14, 2021 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the Coronaviridae family, which is responsible for the COVID-19 pandemic followed by unprecedented global societal and economic disruptive impact. The innate immune system is t ... Full text Link to item Cite

The Disruption of the Endothelial Barrier Contributes to Acute Lung Injury Induced by Coxsackievirus A2 Infection in Mice.

Journal Article Int J Mol Sci · September 13, 2021 Sporadic occurrences and outbreaks of hand, foot, and mouth disease (HFMD) caused by Coxsackievirus A2 (CVA2) have frequently reported worldwide recently, which pose a great challenge to public health. Epidemiological studies have suggested that the main c ... Full text Link to item Cite

Coxsackievirus A2 Leads to Heart Injury in a Neonatal Mouse Model.

Journal Article Viruses · August 11, 2021 Coxsackievirus A2 (CVA2) has emerged as an active pathogen that has been implicated in hand, foot, and mouth disease (HFMD) and herpangina outbreaks worldwide. It has been reported that severe cases with CVA2 infection develop into heart injury, which may ... Full text Link to item Cite

Cardiac arrest and resuscitation activates the hypothalamic-pituitary-adrenal axis and results in severe immunosuppression.

Journal Article J Cereb Blood Flow Metab · May 2021 In patients who are successfully resuscitated after initial cardiac arrest (CA), mortality and morbidity rates are high, due to ischemia/reperfusion injury to the whole body including the nervous and immune systems. How the interactions between these two c ... Full text Open Access Link to item Cite

Essential Role of Non-Coding RNAs in Enterovirus Infection: From Basic Mechanisms to Clinical Prospects.

Journal Article Int J Mol Sci · March 12, 2021 Enteroviruses (EVs) are common RNA viruses that can cause various types of human diseases and conditions such as hand, foot, and mouth disease (HFMD), myocarditis, meningitis, sepsis, and respiratory disorders. Although EV infections in most patients are g ... Full text Link to item Cite

Pathogenesis Study of Enterovirus 71 Using a Novel Human SCARB2 Knock-In Mouse Model.

Journal Article mSphere · March 10, 2021 Enterovirus 71 (EV71) can cause a severe hand-foot-mouth disease in children. However, the precise mechanism of EV71-associated disease, particularly the neuropathogenesis and pulmonary disorder, is still not fully understood because no suitable animal mod ... Full text Link to item Cite

Spontaneous Differentiation of T Follicular Helper Cells in LATY136F Mutant Mice.

Journal Article Front Immunol · 2021 Mice with a mutation at the LAT-PLCγ1 binding site (Y136) have a defect in thymocyte development due to dampened TCR signaling. CD4+ T cells that do reach the periphery are hyper-activated and skewed to Th2. Over time, these mice develop an autoimmune-like ... Full text Link to item Cite

Neonatal Murine Model of Coxsackievirus A2 Infection for the Evaluation of Antiviral Therapeutics and Vaccination.

Journal Article Front Microbiol · 2021 Coxsackievirus (CV) A2 has emerged as an important etiological agent in the pathogen spectrum of hand, foot, and mouth disease (HFMD). The symptoms of CVA2 infections are generally mild, but worsen rapidly in some people, posing a serious threat to childre ... Full text Link to item Cite

Pathological Features of Enterovirus 71-Associated Brain and Lung Damage in Mice Based on Quantitative Proteomic Analysis.

Journal Article Front Microbiol · 2021 The outbreaks of enterovirus 71 (EV71)-associated hand, foot, and mouth disease (HFMD) have emerged as an emergency of global health due to its association with fatal encephalitis and subsequent neurogenic pulmonary edema; however, the molecular characteri ... Full text Link to item Cite

Endothelial activation and dysfunction in COVID-19: from basic mechanisms to potential therapeutic approaches.

Journal Article Signal Transduct Target Ther · December 24, 2020 On 12 March 2020, the outbreak of coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization. As of 4 August 2020, more than 18 million confirmed infections had been reported globally. Most patients have mild symptoms, but ... Full text Link to item Cite

MCC950, a selective NLPR3 inflammasome inhibitor, improves neurologic function and survival after cardiac arrest and resuscitation.

Journal Article J Neuroinflammation · August 31, 2020 BACKGROUND: Cardiac arrest (CA) is associated with high morbidity and mortality, even after spontaneous circulation is re-established. This dire situation is partly due to post-CA syndrome for which no specific and effective intervention is available. One ... Full text Open Access Link to item Cite

Extended ORF8 Gene Region Is Valuable in the Epidemiological Investigation of Severe Acute Respiratory Syndrome-Similar Coronavirus.

Journal Article J Infect Dis · June 29, 2020 Severe acute respiratory syndrome coronavirus (SARS-CoV) was discovered as a novel pathogen in the 2002-2003 SARS epidemic. The emergence and disappearance of this pathogen have brought questions regarding its source and evolution. Within the genome sequen ... Full text Link to item Cite

Virology, Epidemiology, Pathogenesis, and Control of COVID-19.

Journal Article Viruses · March 27, 2020 The outbreak of emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) in China has been brought to global attention and declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Scientific advancements ... Full text Link to item Cite

Hydrogen peroxide sensor HPCA1 is an LRR receptor kinase in Arabidopsis.

Journal Article Nature · February 2020 Featured Publication Hydrogen peroxide (H2O2) is a major reactive oxygen species in unicellular and multicellular organisms, and is produced extracellularly in response to external stresses and internal cues1-4. H2O2 enters cells through aquaporin membrane proteins and covalen ... Full text Link to item Cite

Slow phosphorylation of a tyrosine residue in LAT optimizes T cell ligand discrimination.

Journal Article Nat Immunol · November 2019 Featured Publication Self-non-self discrimination is central to T cell-mediated immunity. The kinetic proofreading model can explain T cell antigen receptor (TCR) ligand discrimination; however, the rate-limiting steps have not been identified. Here, we show that tyrosine phos ... Full text Link to item Cite

Fine particulate matter (PM2.5) enhances FcεRI-mediated signaling and mast cell function.

Journal Article Cell Signal · May 2019 Persistent exposure to ambient fine particulate matter (PM2.5) can exacerbate allergic diseases in humans. Mast cells play an important role in allergic inflammation in peripheral tissues, such as skin, mucosa, and lung. Engagement of the high-affinity Fc ... Full text Link to item Cite

Mast cells contribute to Enterovirus 71 infection-induced pulmonary edema in neonatal mice.

Journal Article Lab Invest · August 2018 Enterovirus (EV) 71 infection has been widely acknowledged as the leading cause of severe hand, foot and mouth disease (HFMD), which may rapidly lead to fatal pulmonary edema. In this study, we established a mouse model for EV71 infection exhibiting high i ... Full text Link to item Cite

Phospholipase D in TCR-Mediated Signaling and T Cell Activation.

Journal Article J Immunol · March 15, 2018 Featured Publication Phospholipase D (PLD) is an enzyme that catalyzes the hydrolysis of phosphatidylcholine, the major phospholipid in the plasma membrane, to generate an important signaling lipid, phosphatidic acid. Phosphatidic acid is a second messenger that regulates vesi ... Full text Link to item Cite

Tonic LAT-HDAC7 Signals Sustain Nur77 and Irf4 Expression to Tune Naive CD4 T Cells.

Journal Article Cell Rep · May 23, 2017 CD4+ T cells differentiate into T helper cell subsets in feedforward manners with synergistic signals from the T cell receptor (TCR), cytokines, and lineage-specific transcription factors. Naive CD4+ T cells avoid spontaneous engagement of feedforward mech ... Full text Link to item Cite

Differential Roles of Phospholipase D Proteins in FcεRI-Mediated Signaling and Mast Cell Function.

Journal Article J Immunol · November 1, 2015 Featured Publication Phospholipase D (PLD) proteins are enzymes that catalyze the hydrolysis of phosphatidylcholine to generate an important signaling lipid, phosphatidic acid. Phosphatidic acid is a putative second messenger implicated in the regulation of vesicular trafficki ... Full text Link to item Cite

Differential Requirements of TCR Signaling in Homeostatic Maintenance and Function of Dendritic Epidermal T Cells.

Journal Article J Immunol · November 1, 2015 Dendritic epidermal T cells (DETCs) are generated exclusively in the fetal thymus and maintained in the skin epithelium throughout postnatal life of the mouse. DETCs have restricted antigenic specificity as a result of their exclusive usage of a canonical ... Full text Link to item Cite

The Importance of IL-6 in the Development of LAT-Mediated Autoimmunity.

Journal Article J Immunol · July 15, 2015 Featured Publication Linker for activation of T cells (LAT) is a transmembrane adaptor protein that is highly tyrosine phosphorylated upon engagement of the TCR. Phosphorylated LAT binds Grb2, Gads, and phospholipase C (PLC)γ1 to mediate T cell activation, proliferation, and c ... Full text Link to item Cite

Molecular evolutionary and structural analysis of the cytosolic DNA sensor cGAS and STING.

Journal Article Nucleic Acids Res · July 2014 Cyclic GMP-AMP (cGAMP) synthase (cGAS) is recently identified as a cytosolic DNA sensor and generates a non-canonical cGAMP that contains G(2',5')pA and A(3',5')pG phosphodiester linkages. cGAMP activates STING which triggers innate immune responses in mam ... Full text Link to item Cite

The role of LAT-PLCγ1 interaction in γδ T cell development and homeostasis.

Journal Article J Immunol · March 15, 2014 Featured Publication LAT is a transmembrane adaptor protein that is vital for integrating TCR-mediated signals to modulate T cell development, activation, and proliferation. Upon T cell activation, LAT is phosphorylated and associates with Grb2, Gads, and PLCγ1 through its fou ... Full text Link to item Cite

Molecular editing of cellular responses by the high-affinity receptor for IgE.

Journal Article Science · February 28, 2014 Cellular responses elicited by cell surface receptors differ according to stimulus strength. We investigated how the high-affinity receptor for immunoglobulin E (IgE) modulates the response of mast cells to a high- or low-affinity stimulus. Both high- and ... Full text Link to item Cite

LAB/NTAL facilitates fungal/PAMP-induced IL-12 and IFN-γ production by repressing β-catenin activation in dendritic cells.

Journal Article PLoS Pathog · May 2013 Fungal pathogens elicit cytokine responses downstream of immunoreceptor tyrosine-based activation motif (ITAM)-coupled or hemiITAM-containing receptors and TLRs. The Linker for Activation of B cells/Non-T cell Activating Linker (LAB/NTAL) encoded by Lat2, ... Full text Link to item Cite

Murine natural killer immunoreceptors use distinct proximal signaling complexes to direct cell function.

Journal Article Blood · April 18, 2013 Signaling pathways leading to natural killer (NK)-cell effector function are complex and incompletely understood. Here, we investigated the proximal signaling pathways downstream of the immunotyrosine-based activation motif (ITAM) bearing activating recept ... Full text Link to item Cite

The requirement of linker for activation of T cells in the primary and memory responses of CD8 T cells.

Journal Article J Immunol · March 15, 2013 Featured Publication Linker for activation of T cells (LAT) is a transmembrane adaptor protein that links TCR engagement to downstream signaling events. Although it is clear that LAT is essential in thymocyte development and initiation of T cell activation, its function during ... Full text Link to item Cite

The importance of the Erk pathway in the development of linker for activation of T cells-mediated autoimmunity.

Journal Article J Immunol · October 15, 2012 Featured Publication The ability of the transmembrane adaptor protein linker for activation of T cells (LAT) to regulate T cell development, activation, survival, and homeostasis depends upon phosphorylation of its multiple tyrosine residues. The mutation of tyrosine 136 on LA ... Full text Link to item Cite

Differential requirement of RasGRP1 for γδ T cell development and activation.

Journal Article J Immunol · July 1, 2012 γδ T (γδT) cells belong to a distinct T cell lineage that performs immune functions different from αβ T (αβT) cells. Previous studies established that Erk1/2 MAPKs are critical for positive selection of αβT cells. Additional evidence suggests that increase ... Full text Link to item Cite

Role of LAT in the granule-mediated cytotoxicity of CD8 T cells.

Journal Article Mol Cell Biol · July 2012 Featured Publication Linker for activation of T cells (LAT) is a transmembrane adaptor protein that is essential to bridge T cell receptor (TCR) engagement to downstream signaling events. The indispensable role of LAT in thymocyte development and T cell activation has been wel ... Full text Link to item Cite

Tyrosine phosphorylation-independent regulation of lipopolysaccharide-mediated response by the transmembrane adaptor protein LAB.

Journal Article J Immunol · March 15, 2012 Featured Publication Linker for activation of B cells (LAB)/non-T cell activation linker is a transmembrane adaptor protein that functions in immunoreceptor-mediated signaling. Published studies have shown that LAB has both positive and negative roles in regulating TCR and hig ... Full text Link to item Cite

The role of Ras guanine nucleotide releasing protein 4 in Fc epsilonRI-mediated signaling, mast cell function, and T cell development.

Journal Article J Biol Chem · March 9, 2012 Featured Publication The RasGRP (Ras guanine nucleotide-releasing protein) family proteins are guanine nucleotide exchange factors that activate Ras GTPases, ultimately leading to MAPK activation and many cellular processes. The RasGRP family has four members. Published studie ... Full text Link to item Cite

Regulation of RasGRP1 function in T cell development and activation by its unique tail domain.

Journal Article PLoS One · 2012 The Ras-guanyl nucleotide exchange factor RasGRP1 plays a critical role in T cell receptor-mediated Erk activation. Previous studies have emphasized the importance of RasGRP1 in the positive selection of thymocytes, activation of T cells, and control of au ... Full text Link to item Cite

Regulation of Erk activation in T cells through the tail domain of RasGRP1

Conference JOURNAL OF IMMUNOLOGY · April 1, 2011 Featured Publication Link to item Cite

LAT-independent triggering of granule-mediated cytotoxicity of CD8 T cells

Conference JOURNAL OF IMMUNOLOGY · April 1, 2011 Featured Publication Link to item Cite

A tale of two TRAPs: LAT and LAB in the regulation of lymphocyte development, activation, and autoimmunity.

Journal Article Immunol Res · April 2011 Transmembrane adaptor proteins (TRAPs) link antigen receptor engagement to downstream cellular processes. Although these proteins typically lack intrinsic enzymatic activity, they are phosphorylated on multiple tyrosine residues following lymphocyte activa ... Full text Link to item Cite

Basal LAT-diacylglycerol-RasGRP1 signals in T cells maintain TCRα gene expression.

Journal Article PLoS One · 2011 In contrast to the well-characterized T cell receptor (TCR) signaling pathways that induce genes that drive T cell development or polarization of naïve CD4 T cells into the diverse T(H)1, T(H)2, T(H)17 and T(reg) lineages, it is unclear what signals mainta ... Full text Link to item Cite

The importance of LAT in the activation, homeostasis, and regulatory function of T cells.

Journal Article J Biol Chem · November 12, 2010 Featured Publication LAT (linker for activation of T cells) is a transmembrane adaptor protein that plays an essential role in TCR-mediated signaling and thymocyte development. Because LAT-deficient mice have an early block in thymocyte development, we utilized an inducible sy ... Full text Link to item Cite

Independent and cooperative roles of adaptor molecules in proximal signaling during FcepsilonRI-mediated mast cell activation.

Journal Article Mol Cell Biol · September 2010 Activation through FcepsilonRI, a high-affinity IgE-binding receptor, is critical for mast cell function during allergy. The formation of a multimolecular proximal signaling complex nucleated by the adaptor molecules SLP-76 and LAT1 is required for activat ... Full text Link to item Cite

The role of the LAT-PLC-gamma1 interaction in T regulatory cell function.

Journal Article J Immunol · March 1, 2010 Featured Publication The interaction between the linker for activation of T cells (LAT) with PLC-gamma1 is important for TCR-mediated Ca(2+) signaling and MAPK activation. Knock-in mice harboring a mutation at the PLC-gamma1 binding site (Y136) of LAT develop a severe lymphopr ... Full text Link to item Cite

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.

Journal Article J Biol Chem · January 29, 2010 Triggering receptor expressed on myeloid cells-2 (TREM-2) is rapidly emerging as a key regulator of the innate immune response via its regulation of macrophage inflammatory responses. Here we demonstrate that proximal TREM-2 signaling parallels other DAP12 ... Full text Link to item Cite

Vav and Rac activation in B cell antigen receptor endocytosis involves Vav recruitment to the adapter protein LAB.

Journal Article J Biol Chem · December 25, 2009 The signal transduction events supporting B cell antigen receptor (BCR) endocytosis are not well understood. We have identified a pathway supporting BCR internalization that begins with tyrosine phosphorylation of the adapter protein LAB. Phosphorylated LA ... Full text Link to item Cite

Regulation of lymphocyte development and activation by the LAT family of adapter proteins.

Journal Article Immunol Rev · November 2009 Transmembrane adapter proteins (TRAPs) are critical components of signaling pathways in lymphocytes, linking antigen receptor engagement to downstream cellular processes. While these proteins lack intrinsic enzymatic activity, their phosphorylation followi ... Full text Link to item Cite

B cell antigen receptor endocytosis and antigen presentation to T cells require Vav and dynamin.

Journal Article J Biol Chem · September 4, 2009 Antigen binding to the B cell antigen receptor (BCR) initiates an array of signaling events. These include endocytosis of ligand-receptor complexes via clathrin-coated pits, trafficking of the internalized ligand to lysosomes, degradation of the associated ... Full text Link to item Cite

Palmitoylation-dependent plasma membrane transport but lipid raft-independent signaling by linker for activation of T cells.

Journal Article J Immunol · August 1, 2009 Linker for activation of T cells (LAT) is a dually palmitoylated transmembrane adaptor protein essential for T cell development and activation. However, whether LAT palmitoylation and/or lipid raft localization are required for its function is controversia ... Full text Link to item Cite

The importance of Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons sterile-alpha motif domain in thymic selection and T-cell activation.

Journal Article Blood · July 2, 2009 Featured Publication The Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons (SLP-76) is a cytosolic adaptor protein essential for thymocyte development and T-cell activation. It contains a sterile-alpha motif (SAM) domain, 3 phosphotyrosine motifs, a p ... Full text Link to item Cite

The essential role of LAT in thymocyte development during transition from the double-positive to single-positive stage.

Journal Article J Immunol · May 1, 2009 Featured Publication The linker for activation of T cells (LAT) is an adaptor protein that couples TCR engagement to downstream signaling cascades. LAT is important in early thymocyte development as LAT-deficient mice have a complete block at the double-negative (DN) 3 stage. ... Full text Link to item Cite

Negative regulation of TCR signaling by linker for activation of X cells via phosphotyrosine-dependent and -independent mechanisms.

Journal Article J Immunol · November 15, 2008 The activation of T cells and the initiation of an immune response is tightly controlled through the crosstalk of both positive and negative regulators. Two adaptors that function as negative regulators of T cell activation are adaptor in lymphocytes of un ... Full text Link to item Cite

Analysis of the linker for activation of T cells and the linker for activation of B cells in natural killer cells reveals a novel signaling cassette, dual usage in ITAM signaling, and influence on development of the Ly49 repertoire.

Journal Article Blood · October 1, 2008 The linker for activation of T cells (LAT) and the linker for activation of B cells (LAB/NTAL/LAT2) are integral proteins in receptor coupling to downstream events. Both proteins are expressed in natural killer (NK) cells and LAT is phosphorylated during t ... Full text Link to item Cite

Identification of a new transmembrane adaptor protein that constitutively binds Grb2 in B cells.

Journal Article J Leukoc Biol · September 2008 Featured Publication Transmembrane adaptor proteins couple antigen receptor engagement to downstream signaling cascades in lymphocytes. One example of these proteins is the linker for activation of T cells (LAT), which plays an indispensable role in T cell activation and devel ... Full text Link to item Cite

LAT Plays Important Role in Thymocyte Survival and Mature T Cell Activation

Conference JOURNAL OF IMMUNOLOGY · April 1, 2007 Featured Publication Link to item Cite

Mouse TCRalphabeta+CD8alphaalpha intraepithelial lymphocytes express genes that down-regulate their antigen reactivity and suppress immune responses.

Journal Article J Immunol · April 1, 2007 Mouse small intestine intraepithelial lymphocytes (IEL) that express alphabetaTCR and CD8alphaalpha homodimers are an enigmatic T cell subset, as their specificity and in vivo function remain to be defined. To gain insight into the nature of these cells, w ... Full text Link to item Cite

An essential role for RasGRP1 in mast cell function and IgE-mediated allergic response.

Journal Article J Exp Med · January 22, 2007 Featured Publication Cross-linking of the FcepsilonRI activates the phosphatidyl inositol 3 kinase (PI3K) and mitogen-activated protein kinase pathways. Previous studies demonstrate that Ras guanyl nucleotide-releasing protein (RasGRP)1 is essential in T cell receptor-mediated ... Full text Link to item Cite

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.

Journal Article Int Immunol · January 2007 Linker for activation of B cell (LAB)/non-T cell activation linker (NTAL) and phosphoprotein associated with glycophospholipid-enriched membrane microdomain (PAG)/Csk-binding protein (Cbp) are raft-associated transmembrane adaptor proteins with distinct fu ... Full text Link to item Cite

Negative regulation of T cell activation and autoimmunity by the transmembrane adaptor protein LAB.

Journal Article Immunity · November 2006 Featured Publication LAB (linker for activation of B cells), also known as NTAL (non-T cell activation linker), is a LAT (linker for activation of T cells)-like adaptor protein that is expressed in B, NK, and mast cells. Its role in lymphocytes has not been clearly demonstrate ... Full text Link to item Cite

Negative regulation of Fc epsilonRI-mediated signaling and mast cell function by the adaptor protein LAX.

Journal Article J Biol Chem · July 7, 2006 Featured Publication LAX is a transmembrane adaptor protein that is expressed in both T and B cells. Upon stimulation via the antigen receptors, it is tyrosine-phosphorylated and binds Grb2 and the p85 subunit of phosphatidylinositol 3-kinase. Disruption of the Lax gene causes ... Full text Link to item Cite

LAT-mediated signaling in CD4+CD25+ regulatory T cell development.

Journal Article J Exp Med · January 23, 2006 Featured Publication Engagement of the T cell receptor for antigen (TCR) induces formation of signaling complexes mediated through the transmembrane adaptor protein, the linker for activation of T cells (LAT). LAT plays an important role in T cell development, activation, and ... Full text Link to item Cite

Negative regulation of lymphocyte activation by the adaptor protein LAX.

Journal Article J Immunol · May 1, 2005 Featured Publication The membrane-associated adaptor protein LAX is a linker for activation of T cells (LAT)-like molecule that is expressed in lymphoid tissues. Upon stimulation of T or B cells, it is phosphorylated and interacts with Grb2 and the p85 subunit of PI3K. LAX, ho ... Full text Link to item Cite

Cutting Edge: Localization of linker for activation of T cells to lipid rafts is not essential in T cell activation and development.

Journal Article J Immunol · January 1, 2005 Featured Publication It has been proposed that upon T cell activation, linker for activation of T cells (LAT), a transmembrane adaptor protein localized to lipid rafts, orchestrates formation of multiprotein complexes and activates signaling cascades in lipid rafts. However, w ... Full text Link to item Cite

Positive and negative regulation of FcepsilonRI-mediated signaling by the adaptor protein LAB/NTAL.

Journal Article J Exp Med · October 18, 2004 Featured Publication Linker for activation of B cells (LAB, also called NTAL; a product of wbscr5 gene) is a newly identified transmembrane adaptor protein that is expressed in B cells, NK cells, and mast cells. Upon BCR activation, LAB is phosphorylated and interacts with Grb ... Full text Link to item Cite

An important role of phospholipase Cgamma1 in pre-B-cell development and allelic exclusion.

Journal Article EMBO J · October 13, 2004 Phospholipase Cgamma1 (PLCgamma1) has been reported to be expressed predominantly in T cells and to play an important role in T-cell receptor signaling. Here we show that PLCgamma1 is expressed throughout B-cell development, with high expression in B-cell ... Full text Link to item Cite

Requirement for Abl kinases in T cell receptor signaling.

Journal Article Curr Biol · July 27, 2004 BACKGROUND: The c-Abl and Arg proteins comprise a unique family of nonreceptor tyrosine kinases that have been implicated in the regulation of cell proliferation and survival, cytoskeletal reorganization, cell migration, and the response to oxidative stres ... Full text Link to item Cite

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 Article J Immunol · June 1, 2004 Featured Publication Adaptor proteins have important functions in coupling stimulation through immunoreceptors with downstream events. The adaptor linker for activation of B cells (LAB)/non-T cell activation linker (NTAL) is expressed in various immune cell types and has a sim ... Full text Link to item Cite

The importance of three membrane-distal tyrosines in the adaptor protein NTAL/LAB.

Journal Article J Biol Chem · March 19, 2004 Featured Publication NTAL (non-T cell activation linker)/LAB (linker for activation of B cells) is a LAT (linker for activation of T cells)-like molecule that is expressed in B cells, mast cells, natural killer cells, and monocytes. Upon engagement of the B cell receptor or Fc ... Full text Link to item Cite

Adaptor proteins in lymphocyte activation.

Journal Article Curr Opin Immunol · June 2003 Adaptor proteins are unique, as they contain modular domains and lack intrinsic enzymatic activity. These proteins are scaffolds for the organization of macromolecular complexes and they recruit other proteins for correct localization during molecular sign ... Full text Link to item Cite

LAB: a new membrane-associated adaptor molecule in B cell activation.

Journal Article Nat Immunol · February 2003 Featured Publication The adaptor molecule, linker for activation of T cells (LAT), is essential in T cell activation and development; a similar molecule in B cells has not yet been identified. Here, we report the identification of a new adaptor protein, linker for activation o ... Full text Link to item Cite

Minimal requirement of tyrosine residues of linker for activation of T cells in TCR signaling and thymocyte development.

Journal Article J Immunol · January 1, 2003 Featured Publication Linker for activation of T cells (LAT) is a membrane-associated adaptor protein that is phosphorylated on multiple tyrosines upon TCR cross-linking. Previous studies show that LAT is essential for TCR-mediated signaling and thymocyte development. In this s ... Full text Link to item Cite

Molecular cloning of a novel gene encoding a membrane-associated adaptor protein (LAX) in lymphocyte signaling.

Journal Article J Biol Chem · November 29, 2002 Featured Publication Membrane-associated adaptors play an important role in coupling antigen receptor engagement to downstream signaling events, such as Ras-MAPK activation, Ca(2+) flux, and nuclear factor of activated T cells (NFAT) activation. Here we identified a novel memb ... Full text Link to item Cite

Knock-in mutation of the distal four tyrosines of linker for activation of T cells blocks murine T cell development.

Journal Article J Exp Med · July 16, 2001 The integral membrane adapter protein linker for activation of T cells (LAT) performs a critical function in T cell antigen receptor (TCR) signal transduction by coupling the TCR to downstream signaling pathways. After TCR engagement, LAT is tyrosine phosp ... Full text Link to item Cite

Dynamic actin polymerization drives T cell receptor-induced spreading: a role for the signal transduction adaptor LAT.

Journal Article Immunity · March 2001 T cell activation induces functional changes in cell shape and cytoskeletal architecture. To facilitate the collection of dynamic, high-resolution images of activated T cells, we plated T cells on coverslips coated with antibodies to the T cell receptor (T ... Full text Link to item Cite

Signaling via LAT (linker for T-cell activation) and Syk/ZAP70 is required for ERK activation and NFAT transcriptional activation following CD2 stimulation.

Journal Article Blood · September 15, 2000 Activation of T cells can be initiated through cell surface molecules in addition to the T-cell receptor-CD3 (TCR-CD3) complex. In human T cells, ligation of the CD2 molecule by mitogenic pairs of anti-CD2 monoclonal antibodies activates T cells via bioche ... Link to item Cite

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.

Journal Article J Biol Chem · July 28, 2000 Featured Publication The linker for activation of T cells (LAT) is a critical adaptor molecule required for T cell antigen receptor (TCR)-mediated signaling and thymocyte development. Upon T cell activation, LAT becomes highly phosphorylated on tyrosine residues, and Grb2, Gad ... Full text Link to item Cite

LAT is essential for Fc(epsilon)RI-mediated mast cell activation.

Journal Article Immunity · May 2000 The linker molecule LAT is a substrate of the tyrosine kinases activated following TCR engagement of T cells. LAT is also expressed in platelets, NK, and mast cells. Although LAT-deficient mice contain normal numbers of mast cells, we found that LAT-defici ... Full text Link to item Cite

The role of membrane-associated adaptors in T cell receptor signalling.

Journal Article Semin Immunol · February 2000 Engagement of the T cell receptor leads to activation of several tyrosine kinases and phosphorylation of many intracellular proteins. This is followed by Ca2+ mobilization and activation of multiple biochemical pathways, including the Ras/MAPK cascade, and ... Full text Link to item Cite

LAT is required for tyrosine phosphorylation of phospholipase cgamma2 and platelet activation by the collagen receptor GPVI.

Journal Article Mol Cell Biol · December 1999 Featured Publication In the present study, we have addressed the role of the linker for activation of T cells (LAT) in the regulation of phospholipase Cgamma2 (PLCgamma2) by the platelet collagen receptor glycoprotein VI (GPVI). LAT is tyrosine phosphorylated in human platelet ... Full text Link to item Cite

Association of the adaptor molecule LAT with CD4 and CD8 coreceptors identifies a new coreceptor function in T cell receptor signal transduction.

Journal Article J Exp Med · November 15, 1999 Featured Publication Linker for activation of T cells (LAT) is an adaptor protein whose tyrosine phosphorylation is critical for transduction of the T cell receptor (TCR) signal. LAT phosphorylation is accomplished by the protein tyrosine kinase ZAP-70, but it is not at all cl ... Full text Link to item Cite

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.

Journal Article J Biol Chem · September 24, 1999 Stimulation of the T cell antigen receptor (TCR) induces tyrosine phosphorylation of numerous intracellular proteins. We have recently investigated the role of the adaptor protein Shb in the early events of T cell signaling and observed that Shb associates ... Full text Link to item Cite

Functional analysis of LAT in TCR-mediated signaling pathways using a LAT-deficient Jurkat cell line.

Journal Article Int Immunol · June 1999 Featured Publication The adaptor molecule LAT (linker for activation of T cells) is a palmitoylated integral membrane protein that localizes to the glycolipid-enriched microdomains in the plasma membrane. Upon TCR engagement, LAT becomes phosphorylated on multiple tyrosine res ... Full text Link to item Cite

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.

Journal Article Am J Pathol · April 1999 LAT (linker for activation of T cells) is an integral membrane protein of 36-38 kd that plays an important role in T cell activation. Using a rabbit polyclonal antibody generated against the cytosolic portion of LAT, we investigated the immunohistochemical ... Full text Link to item Cite

Essential role of LAT in T cell development.

Journal Article Immunity · March 1999 Featured Publication The linker molecule LAT is a substrate of the tyrosine kinases activated following TCR engagement. Phosphorylated LAT binds many critical signaling molecules. The central role of this molecule in TCR-mediated signaling has been demonstrated by experiments ... Full text Link to item Cite

Cutting edge: a role for the adaptor protein LAT in human NK cell-mediated cytotoxicity.

Journal Article J Immunol · March 1, 1999 Stimulation of NK cell-mediated cytotoxicity involves the coupling of proximal Src and Syk family protein tyrosine kinases to downstream effectors. However, the mechanisms linking these second messenger pathways are incompletely understood. Here, we descri ... Link to item Cite

Studies on the adapter molecule LAT.

Journal Article Cold Spring Harb Symp Quant Biol · 1999 Full text Link to item Cite

Molecular basis of T cell inactivation by CTLA-4.

Journal Article Science · December 18, 1998 CTLA-4, a negative regulator of T cell function, was found to associate with the T cell receptor (TCR) complex zeta chain in primary T cells. The association of TCRzeta with CTLA-4, reconstituted in 293 transfectants, was enhanced by p56(lck)-induced tyros ... Full text Link to item Cite

LAT is required for TCR-mediated activation of PLCgamma1 and the Ras pathway.

Journal Article Immunity · November 1998 In this study, we present the further characterization of a mutant Jurkat T cell line, J.CaM2, that is defective in TCR-mediated signal transduction. Although initial TCR-mediated signaling events such as the inducible tyrosine phosphorylation of the TCR-z ... Full text Link to item Cite

LAT palmitoylation: its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation.

Journal Article Immunity · August 1998 Featured Publication The linker molecule LAT is a critical substrate of the tyrosine kinases activated upon TCR engagement. Phosphorylated LAT binds Grb2, PLC-gamma1, and other signaling molecules. We demonstrate that human LAT is palmitoylated and that palmitoylated LAT predo ... Full text Link to item Cite

ZAP-70-dependent and -independent activation of Erk in Jurkat T cells. Differences in signaling induced by H2o2 and Cd3 cross-linking.

Journal Article J Biol Chem · April 24, 1998 Oxidative stress in T cells induces signaling events similar to those initiated by T cell antigen receptor engagement, including tyrosine phosphorylation and activation of the critical protein-tyrosine kinase ZAP-70. Distal signaling events such as the act ... Full text Link to item Cite

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.

Journal Article Mol Cell Biol · March 1998 T-cell antigen receptor (TCR) engagement activates multiple protein tyrosine kinases (PTKs), including the Src family member, Lck, and the Syk-related PTK, ZAP-70. Studies in ZAP-70-deficient humans have demonstrated that ZAP-70 plays crucial roles in T-ce ... Full text Link to item Cite

LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation.

Journal Article Cell · January 9, 1998 Featured Publication Despite extensive study, several of the major components involved in T cell receptor-mediated signaling remain unidentified. Here we report the cloning of the cDNA for a highly tyrosine-phosphorylated 36-38 kDa protein, previously characterized by its asso ... Full text Link to item Cite

Regulation of ZAP-70 intracellular localization: visualization with the green fluorescent protein.

Journal Article J Exp Med · November 17, 1997 To investigate the cellular dynamics of ZAP-70, we have studied the distribution and regulation of its intracellular location using a ZAP-70 green fluorescent protein chimera. Initial experiments in epithelial cells indicated that ZAP-70 is diffusely locat ... Full text Link to item Cite

ZAP-70 tyrosine kinase is required for the up-regulation of Fas ligand in activation-induced T cell apoptosis.

Journal Article J Immunol · August 1, 1997 Activation-induced cell death (AICD) is initiated by the TCR-dependent up-regulation of Fas ligand (FasL) mRNA. The subsequently generated soluble or cell-associated FasL gene products bind Fas, leading to apoptosis of the T cells. Although TCR stimulation ... Link to item Cite

MHC class I-peptide interactions and TCR recognition.

Journal Article Cancer Surv · 1995 The recent crystal structure determinations of MHC class I molecules with single bound peptides have allowed us to understand the guidelines that govern peptide binding in a given MHC allele. Evolution has provided for MHC class I molecules whose antigen b ... Link to item Cite

The three-dimensional structure of H-2Db at 2.4 A resolution: implications for antigen-determinant selection.

Journal Article Cell · January 14, 1994 Featured Publication Solution at 2.4 A resolution of the structure of H-2Db with the influenza virus peptide NP366-374 (ASNEN-METM) and comparison with the H-2Kb-VSV (RGY-VYQGL) structure allow description of the molecular details of MHC class I peptide binding interactions fo ... Full text Link to item Cite

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.

Journal Article Proc Natl Acad Sci U S A · September 1, 1992 Featured Publication To study the structure of a homogenous major histocompatibility complex (MHC) class I molecule containing a single bound peptide, a complex of recombinant mouse H-2Kb, beta 2-microglobulin (beta 2m), and a fragment of the vesicular stomatitis virus (VSV) n ... Full text Link to item Cite