Scholars@Duke
Weiguo Zhang

Weiguo Zhang

Adjunct Associate Professor in the Department of Immunology
Integrative Immunobiology
zhang033@mc.duke.edu
Box 3010 DUMC, 112 Jones Building, Durham, NC 27710
112 Jones Builidng, 207 Resear, Box 3010 DUMC, Durham, NC 27710

Featured Works

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

Journal article Nature · February 2020 Featured Work 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 Work 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

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

Journal article J Immunol · March 15, 2018 Featured Work 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

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

Journal article J Immunol · November 1, 2015 Featured Work 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

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

Journal article J Immunol · July 15, 2015 Featured Work 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

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

Journal article J Immunol · March 15, 2014 Featured Work 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

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 Work 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 Work 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

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

Journal article Mol Cell Biol · July 2012 Featured Work 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 Work 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 Work 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 Erk activation in T cells through the tail domain of RasGRP1

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

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

Conference JOURNAL OF IMMUNOLOGY · April 1, 2011 Featured Work 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 Work 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

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

Journal article J Immunol · March 1, 2010 Featured Work 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 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 Work 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 Work 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

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

Journal article J Leukoc Biol · September 2008 Featured Work 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 Work 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 Work 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

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

Journal article Immunity · November 2006 Featured Work 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 Work 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 Work 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 Work 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 Work 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 Work 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

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 Work 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 Work 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

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

Journal article Nat Immunol · February 2003 Featured Work 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 Work 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 Work 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

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

Journal article Mol Cell Biol · December 1999 Featured Work 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 Work 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

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

Journal article Int Immunol · June 1999 Featured Work 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

Essential role of LAT in T cell development.

Journal article Immunity · March 1999 Featured Work 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

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

Journal article Immunity · August 1998 Featured Work 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

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

Journal article Cell · January 9, 1998 Featured Work 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

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

Journal article Cell · January 14, 1994 Featured Work 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 Work 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