Research Topics
Genomes and Genes
| Pamela L SchwartzbergSummaryAffiliation: National Institutes of Health Country: USA Publications
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Detail Information
Publications
TEC-family kinases: regulators of T-helper-cell differentiationPamela L Schwartzberg
National Human Genome Research Institute, National Institutes of Health, 4A38 49 Convent Drive, Bethesda, Maryland 20892, USA
Nat Rev Immunol 5:284-95. 2005..Here, we review studies of signalling pathways that involve TEC kinases and how these pathways might contribute to the regulation of T-helper-cell differentiation and function...- Formin the wayPamela L Schwartzberg
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
Immunity 26:139-41. 2007..In this issue of Immunity, the functions of two classes of actin nucleators are examined in T lymphocytes, giving insight into the regulation of T cell polarity (Gomez et al., 2007)... 
SLAM receptors and SAP influence lymphocyte interactions, development and functionPamela L Schwartzberg
National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Nat Rev Immunol 9:39-46. 2009..These data have revealed that SLAM family members and SAP have crucial roles in regulating lymphocyte interactions and adhesion, which are required for the normal development, homeostasis and function of the immune system...
Optimal germinal center responses require a multistage T cell:B cell adhesion process involving integrins, SLAM-associated protein, and CD84Jennifer L Cannons
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
Immunity 32:253-65. 2010..Our results reveal insight into the dynamic regulation of T cell:B cell interactions and identify SLAM family members as critical components of sustained T cell:B cell adhesion required for productive humoral immunity...- Biochemical and genetic evidence for a SAP-PKC-theta interaction contributing to IL-4 regulationJennifer L Cannons
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 185:2819-27. 2010.... - SAP regulates T(H)2 differentiation and PKC-theta-mediated activation of NF-kappaB1Jennifer L Cannons
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
Immunity 21:693-706. 2004..SLAM engagement amplified PKC-theta recruitment in wt but not SAP- or Fyn-deficient cells, arguing that a SAP/Fyn-mediated pathway enhances PKC-theta/NF-kappaB1 activation and suggesting a role for this pathway in T(H)2 regulation... 
SAP regulates T cell-mediated help for humoral immunity by a mechanism distinct from cytokine regulationJennifer L Cannons
National Human Genome Research Institute, National Institutes of Health NIH, Bethesda, MD 20892, USA
J Exp Med 203:1551-65. 2006..Thus, SAP affects expression of key molecules required for T-B cell collaboration by mechanisms that are distinct from its role in cytokine regulation...- Requirements for selection of conventional and innate T lymphocyte lineagesReiko Horai
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
Immunity 27:775-85. 2007.... - The major component in schistosome eggs responsible for conditioning dendritic cells for Th2 polarization is a T2 ribonuclease (omega-1)Svenja Steinfelder
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
J Exp Med 206:1681-90. 2009..Based on this evidence, we hypothesize that S. mansoni omega-1 acts by limiting the interaction of DCs with CD4(+) T lymphocytes, thereby lowering the strength of the activation signal delivered... - SAP-controlled T-B cell interactions underlie germinal centre formationHai Qi
Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Nature 455:764-9. 2008..These results offer an explanation for the germinal centre defect due to SAP deficiency and provide new insights into the bi-directional communication between cognate T and B cells in vivo... - Differential expression of interleukin-17A and -17F is coupled to T cell receptor signaling via inducible T cell kinaseJulio Gomez-Rodriguez
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
Immunity 31:587-97. 2009..Our results suggest that Itk specifically couples TCR signaling to Il17a expression and the differential regulation of Th17 cell cytokines through NFATc1... - Altered development of CD8+ T cell lineages in mice deficient for the Tec kinases Itk and RlkChristine Broussard
National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Immunity 25:93-104. 2006..Our results suggest that Tec kinases differentially regulate development of conventional versus nonconventional lymphocytes... - A novel ICOS-independent, but CD28- and SAP-dependent, pathway of T cell-dependent, polysaccharide-specific humoral immunity in response to intact Streptococcus pneumoniae versus pneumococcal conjugate vaccineQuanyi Chen
Department of Pathology, Uniformed Services University of the Health Sciences, National Institutes of Health, Bethesda, MD 20814, USA
J Immunol 181:8258-66. 2008..These data define a novel T cell-, SAP-, and B7-dependent, but ICOS-independent, extrafollicular pathway of Ig induction... - Positive and negative signaling through SLAM receptors regulate synapse organization and thresholds of cytolysisFang Zhao
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
Immunity 36:1003-16. 2012..Hence, SAP and SLAM receptors regulate positive and negative signals required for organizing the T cell:B cell synapse and setting thresholds for cytotoxicity against distinct cellular targets... - Cbl enforces an SLP76-dependent signaling pathway for T cell differentiationY Jeffrey Chiang
Experimental Immunology Branch, NCI, and NIA, National Institutes of Health, Bethesda, Maryland 20892, USA
J Biol Chem 284:4429-38. 2009..Thus, our data demonstrate that Cbl suppresses activation of a bypass signaling pathway and thereby enforces SLP76 dependence of early T cell development... - The immunity-related GTPase Irgm1 promotes the expansion of activated CD4+ T cell populations by preventing interferon-gamma-induced cell deathCarl G Feng
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Nat Immunol 9:1279-87. 2008..Our studies identify a feedback mechanism in the T helper type 1 response that limits the detrimental effects of IFN-gamma on effector T lymphocyte survival while promoting the antimicrobial functions of IFN-gamma... - Functional and epigenetic studies reveal multistep differentiation and plasticity of in vitro-generated and in vivo-derived follicular T helper cellsKristina T Lu
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
Immunity 35:622-32. 2011..ChIP-Seq analyses revealed positive epigenetic markings on Tbx21, Gata3, and Rorc in Tfh-like and ex vivo Tfh cells and on Bcl6 in non-Tfh cells, supporting the concept of plasticity between Tfh and other Th cell populations... - Early Th1 cell differentiation is marked by a Tfh cell-like transitionShingo Nakayamada
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Immunity 35:919-31. 2011..Our data argue that Tfh and Th1 cells share a transitional stage through the signal mediated by STAT4, which promotes both phenotypes. However, T-bet represses Tfh cell functionalities, promoting full Th1 cell differentiation... - Impaired in vitro regulatory T cell function associated with Wiskott-Aldrich syndromeMarsilio Adriani
Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, 49 Convent Dr, Blg 49, Rm 3A20, Bethesda, MD 20892 4442, USA
Clin Immunol 124:41-8. 2007..These findings may provide insights into the complex pathophysiology and paradoxical phenotypes of WAS and suggest new therapeutic modalities for autoimmunity in these patients... - Kinase-independent functions for Itk in TCR-induced regulation of Vav and the actin cytoskeletonDerek Dombroski
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 174:1385-92. 2005..These data suggest a kinase-independent scaffolding function for Itk in the regulation of Vav localization and TCR-induced actin polarization... - Tec kinases regulate TCR-mediated recruitment of signaling molecules and integrin-dependent cell adhesionLisa D Finkelstein
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 175:5923-30. 2005..Thus, Tec kinases play key roles in regulating TCR-mediated polarization of integrins and signaling molecules to the site of TCR stimulation as well as the up-regulation of integrin adhesion... - Advantages of q-PCR as a method of screening for gene targeting in mammalian cells using conventional and whole BAC-based constructsJulio Gomez-Rodriguez
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
Nucleic Acids Res 36:e117. 2008..Our results demonstrate the utility of q-PCR as a screening tool for gene targeting and further highlight potential problems with the use of whole BAC-based constructs for homologous recombination... - CBFB-MYH11 hinders early T-cell development and induces massive cell death in the thymusLing Zhao
Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, 49 Convent Drive, Bethesda, MD 20892, USA
Blood 109:3432-40. 2007..Our data suggest that Cbfb-MYH11 suppressed Cbfb in several stages of T-cell development and provide a mechanism for CBFB-MYH11 association with myeloid but not lymphoid leukemia... - A role for thymic stromal lymphopoietin in CD4(+) T cell developmentAmin Al-Shami
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Exp Med 200:159-68. 2004..Thus, as compared with other known cytokines, TSLP is distinctive in exhibiting a lineage preference for the expansion and survival of CD4(+) T cells... - Fine-tuning lymphocyte regulation: what's new with tyrosine kinases and phosphatases?Jennifer L Cannons
National Human Genome Research Institute, 49 4A38, 49 Convent Drive, National Institutes of Health, Bethesda, MD 20892, USA
Curr Opin Immunol 16:296-303. 2004.... - Tec kinases regulate T-lymphocyte development and function: new insights into the roles of Itk and Rlk/TxkJulie A Readinger
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
Immunol Rev 228:93-114. 2009..We review new findings on the Tec kinases with a focus on their roles in T-cell development and mature T-cell differentiation... - Improved generation of C57BL/6J mouse embryonic stem cells in a defined serum-free mediaJun Cheng
Genetic Diseases Research Branch, National Human Genome Research Institute, Bethesda, Maryland, USA
Genesis 39:100-4. 2004..Our work suggests that the use of defined serum-free media may facilitate the generation of ES cells from inbred mouse strains... - Tec kinases, actin, and cell adhesionJulio Gomez Rodriguez
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
Immunol Rev 218:45-64. 2007.... - The expression of Wiskott-Aldrich syndrome protein (WASP) is dependent on WASP-interacting protein (WIP)Akihiro Konno
Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, 49 Convent Drive, Bethesday, MD 20892, USA
Int Immunol 19:185-92. 2007..These results demonstrate that expression of WIP is necessary for functional WASP expression in human cells and provide a new paradigm for understanding the function of these two molecules... - Constitutive reductions in mTOR alter cell size, immune cell development, and antibody productionShuling Zhang
Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute NIH, Bethesda, MD 20892, USA
Blood 117:1228-38. 2011..Thus, mTOR is required for the maturation and differentiation of multiple immune cell lineages. These mice provide a novel platform for studying the consequences of constitutively reduced mTORC1/TORC2 activity... - Tec kinases: shaping T-cell activation through actinLisa D Finkelstein
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
Trends Cell Biol 14:443-51. 2004..These data, as well as other findings, support roles for Tec kinases in actin cytoskeleton regulation... - A critical role for IL-21 in regulating immunoglobulin productionKatsutoshi Ozaki
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1674, USA
Science 298:1630-4. 2002..This suggests that these gammac-dependent cytokines may be those whose inactivation is primarily responsible for the B cell defect in humans with XSCID... - Tec family kinases Itk and Rlk / Txk in T lymphocytes: cross-regulation of cytokine production and T-cell fatesJulio Gomez-Rodriguez
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
FEBS J 278:1980-9. 2011..Together, these results suggest that the Tec family kinases play critical roles in helping shape immune responses via their effects on the differentiation and function of distinct cytokine-producing, effector T-cell populations... - SLAM family receptors and SAP adaptors in immunityJennifer L Cannons
National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Annu Rev Immunol 29:665-705. 2011..In this review, we cover recent findings on the roles of SLAM family receptors and the SAP family of adaptors, with a focus on their regulation of the pathways involved in the pathogenesis of XLP and other immune disorders... - Regulation of microRNA expression and abundance during lymphopoiesisStefan Kuchen
Genomics and Immunity, NIAMS, NIH, Bethesda, MD 20892, USA
Immunity 32:828-39. 2010..Our data provide a comprehensive map of immunity's microRNome and reveal the underlying epigenetic and transcriptional forces that shape miRNA homeostasis... - A mosaic activating mutation in AKT1 associated with the Proteus syndromeMarjorie J Lindhurst
National Human Genome Research Institute, Bethesda, Maryland, USA
N Engl J Med 365:611-9. 2011..The Proteus syndrome is characterized by the overgrowth of skin, connective tissue, brain, and other tissues. It has been hypothesized that the syndrome is caused by somatic mosaicism for a mutation that is lethal in the nonmosaic state... - Requirement for Tec kinases in chemokine-induced migration and activation of Cdc42 and RacAya Takesono
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
Curr Biol 14:917-22. 2004..Thus, Tec kinases are critical components of signaling pathways required for actin polarization downstream from both antigen and chemokine receptors in T cells... - Rheumatologic and autoimmune manifestations of primary immunodeficiency disordersRamona Goyal
Office of the Clinical Director, NIAMS, National Institutes of Health, Bethesda, Maryland 20892, USA
Curr Opin Rheumatol 21:78-84. 2009.... - Selective targeting of ITK blocks multiple steps of HIV replicationJulie A Readinger
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 105:6684-9. 2008..Our data suggest that inhibition of ITK blocks HIV infection by affecting multiple steps of HIV replication... - Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemiaMarjorie J Lindhurst
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 103:15927-32. 2006.... - Acinar cell apoptosis in Serpini2-deficient mice models pancreatic insufficiencyStacie K Loftus
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
PLoS Genet 1:e38. 2005.... - Essential role for retinoic acid in the promotion of CD4(+) T cell effector responses via retinoic acid receptor alphaJason A Hall
Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Immunity 34:435-47. 2011.... - Balancing selection maintains a form of ERAP2 that undergoes nonsense-mediated decay and affects antigen presentationAida M Andres
Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
PLoS Genet 6:e1001157. 2010..Although the precise selective pressure that maintains polymorphism is unknown, the demonstrated differences between the ERAP2 splice forms provide important insights into the potential mechanism for the action of selection... - Beyond calcium: new signaling pathways for Tec family kinasesAya Takesono
National Human Genome Research Institute, 49 Convent Drive, 49/4A38, National Institutes of Health, Bethesda, MD 20892, USA
J Cell Sci 115:3039-48. 2002..Their impact on cellular physiology suggests that the Tec kinases help regulate multiple cellular processes beyond Ca(2+) mobilization... - Genetic approaches to tyrosine kinase signaling pathways in the immune systemPamela L Schwartzberg
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892 4472, USA
Immunol Res 27:481-8. 2003..As a model system, we are examining the Tec family kinases and their roles in T lymphocyte development and function... - The murine NK receptor 2B4 (CD244) exhibits inhibitory function independent of signaling lymphocytic activation molecule-associated protein expressionJill M Mooney
Graduate Program in Immunology, University of Texas Southwestern Medical Center, Dallas 75390, USA
J Immunol 173:3953-61. 2004..This predominant inhibitory function of murine 2B4 correlates with increased 2B4 long isoform level expression over 2B4 short... - SAP is required for Th cell function and for immunity to influenzaCris Kamperschroer
Trudeau Institute, Saranac Lake, NY 12983, USA
J Immunol 177:5317-27. 2006..Overall, our results demonstrate that SAP is required in CD4 T cells for their ability to help B cell responses and promote influenza-specific immunity... - SAP is required for generating long-term humoral immunityShane Crotty
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
Nature 421:282-7. 2003..Thus, SAP has a crucial role in CD4+ T-cell function: it is essential for late B-cell help and the development of long-term humoral immunity but is not required for early B-cell help and class switching... - T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3Eun Sook Hwang
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA
Science 307:430-3. 2005..These results provide a novel function for tyrosine phosphorylation of a transcription factor in specifying alternate fates of a common progenitor cell... - Molecular and cellular pathogenesis of X-linked lymphoproliferative diseaseKim E Nichols
Pediatric Oncology, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
Immunol Rev 203:180-99. 2005..Further studies of SAP and the SLAM family receptors will provide insights into XLP and elucidate the signaling events regulating lymphocyte ontogeny and function... - SH2D1A regulates T-dependent humoral autoimmunityJonathan D Hron
Washington University School of Medicine, Campus Box 8045, CSRB 6617, 660 S Euclid Ave, St Louis, MO 63110, USA
J Exp Med 200:261-6. 2004.... - TNF-alpha is crucial for the development of autoimmune arthritis in IL-1 receptor antagonist-deficient miceReiko Horai
Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan
J Clin Invest 114:1603-11. 2004..These findings suggest that IL-1 receptor antagonist deficiency in T cells disrupts homeostasis of the immune system and that TNF-alpha plays an important role in activating T cells through induction of OX40... - A BAC contig map of the Ly49 gene cluster in 129 mice reveals extensive differences in gene content relative to C57BL/6 miceAndrew P Makrigiannis
Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute Frederick, Frederick, Maryland 21702 1201, USA
Genomics 79:437-44. 2002..These results indicate that Ly49 gene numbers can be significantly different between inbred mouse strains, analogous to the haplotype differences observed in the human KIR genes... - Binding of SAP SH2 domain to FynT SH3 domain reveals a novel mechanism of receptor signalling in immune regulationSylvain Latour
Laboratory of Molecular Oncology, Clinical Research Institute of Montreal, Montreal, Quebec, H2W 1R7, Canada
Nat Cell Biol 5:149-54. 2003..These observations characterize a biologically important signalling mechanism in which an adaptor molecule composed only of an SH2 domain links a receptor devoid of intrinsic catalytic activity to the kinase required for its function... - Tec family kinases in T lymphocyte development and functionLeslie J Berg
Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
Annu Rev Immunol 23:549-600. 2005..Although they quantitatively reduce proximal signaling, mutations that eliminate Tec family kinases in T cells nonetheless qualitatively alter T cell development and differentiation... - Perturbation of B cell activation in SLAM-associated protein-deficient mice is associated with changes in gammaherpesvirus latency reservoirsIn Jeong Kim
Trudeau Institute, Saranac Lake, NY 12983, USA
J Immunol 178:1692-701. 2007..Furthermore, there were defects in normal latency reservoirs within the germinal center cells and IgD(+)"naive" B cells in SAP-deficient mice, showing a profound effect of the SAP mutation on latency reservoirs... - Regulation of NKT cell development by SAP, the protein defective in XLPKim E Nichols
Pediatric Oncology, Wood, 4th Floor, 3615 Civic Center Boulevard, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
Nat Med 11:340-5. 2005..Thus, SAP is a crucial regulator of NKT cell ontogeny in humans and in mice. The absence of NKT cells may contribute to the phenotypes of SAP deficiency, including abnormal antiviral and antitumor immunity and hypogammaglobulinemia... - Itk functions to control actin polymerization at the immune synapse through localized activation of Cdc42 and WASPChristine M Labno
Department of Pathology, University of Chicago, Chicago, IL 60637, USA
Curr Biol 13:1619-24. 2003..Our results identify Itk as a key element of the pathway leading to localized actin polymerization at the immune synapse... - Functional hierarchy of the N-terminal tyrosines of SLP-76Martha S Jordan
Signal Transduction Program, Leonard and Madlyn Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA
J Immunol 176:2430-8. 2006..These studies show that Tyr(145) of SLP-76 is the most critical tyrosine for both T cell function in vitro and T cell development in vivo...