Arthur Weiss

Summary

Affiliation: University of California
Country: USA

Publications

  1. pmc STIM1, PKC-δ and RasGRP set a threshold for proapoptotic Erk signaling during B cell development
    Andre Limnander
    Department of Medicine, Howard Hughes Medical Institute, Rosalind Russell Medical Research Center for Arthritis, University of California at San Francisco, San Francisco, California, USA
    Nat Immunol 12:425-33. 2011
  2. pmc B cells drive lymphocyte activation and expansion in mice with the CD45 wedge mutation and Fas deficiency
    Vikas A Gupta
    Department of Medicine, Biomedical Sciences Graduate Program, Medical Scientist Training Program, University of California San Francisco, San Francisco, CA 94143, USA
    J Exp Med 205:2755-61. 2008
  3. pmc Inhibition of ZAP-70 kinase activity via an analog-sensitive allele blocks T cell receptor and CD28 superagonist signaling
    Susan E Levin
    Departments of Medicine and Microbiology and Immunology, Biomedical Sciences Graduate Program, and Howard Hughes Medical Institute, University of California San Francisco, 5134 Parnassus Avenue, San Francisco, CA 94143, USA
    J Biol Chem 283:15419-30. 2008
  4. pmc Distinct roles for Syk and ZAP-70 during early thymocyte development
    Emil H Palacios
    Department of Medicine, The Rosalind Russell Medical Research Center for Arthritis, University of California San Francisco, San Francisco, CA 94143, USA
    J Exp Med 204:1703-15. 2007
  5. pmc Twisting tails exposed: the evidence for TCR conformational change
    Susan E Levin
    Rosalind Russell Medical Research Center for Arthritis, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA
    J Exp Med 201:489-92. 2005
  6. pmc The tyrosine phosphatase CD148 is excluded from the immunologic synapse and down-regulates prolonged T cell signaling
    Joseph Lin
    Department of Medicine, Biomedical Sciences Graduate Program, University of California at San Francisco, 533 Parnassus Avenue, Box no 0795, San Francisco, CA 94143 0795, USA
    J Cell Biol 162:673-82. 2003
  7. pmc Phosphoinositide-dependent kinase 1 targets protein kinase A in a pathway that regulates interleukin 4
    Ajay Nirula
    Department of Medicine, The Rosalind Russell Medical Research Center for Arthritis and the Howard Hughes Medical Institute, University of California at San Francisco, CA 94143, USA
    J Exp Med 203:1733-44. 2006
  8. pmc Src-like adaptor protein (SLAP) is a negative regulator of T cell receptor signaling
    T Sosinowski
    Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, California 94143 0795, USA
    J Exp Med 191:463-74. 2000
  9. pmc Antigen receptor signaling in the rheumatic diseases
    Julie Zikherman
    Division of Rheumatology, Rosalind Russell Medical Research Center for Arthritis, Department of Medicine, Howard Hughes Medical Institute, University of California, San Francisco, 513 Parnassus Avenue San Francisco, CA 94143, USA
    Arthritis Res Ther 11:202. 2009
  10. ncbi request reprint Discovering the TCR beta-chain by subtraction
    Arthur Weiss
    Howard Hughes Medical Institute, Department of Medicine, Rosalind Russell Medical Research Center for Arthritis, University of California, San Francisco 94143, USA
    J Immunol 175:2769-70. 2005

Collaborators

Detail Information

Publications76

  1. pmc STIM1, PKC-δ and RasGRP set a threshold for proapoptotic Erk signaling during B cell development
    Andre Limnander
    Department of Medicine, Howard Hughes Medical Institute, Rosalind Russell Medical Research Center for Arthritis, University of California at San Francisco, San Francisco, California, USA
    Nat Immunol 12:425-33. 2011
    ..Conversely, overexpression of STIM1 conferred a competitive disadvantage to developing B cells. Our findings establish Ca(2+)-dependent Erk signaling as a critical proapoptotic pathway that mediates the negative selection of B cells...
  2. pmc B cells drive lymphocyte activation and expansion in mice with the CD45 wedge mutation and Fas deficiency
    Vikas A Gupta
    Department of Medicine, Biomedical Sciences Graduate Program, Medical Scientist Training Program, University of California San Francisco, San Francisco, CA 94143, USA
    J Exp Med 205:2755-61. 2008
    ..These results reveal a requirement for careful control of B cell signaling and cell death in preventing inappropriate lymphocyte activation and autoimmunity...
  3. pmc Inhibition of ZAP-70 kinase activity via an analog-sensitive allele blocks T cell receptor and CD28 superagonist signaling
    Susan E Levin
    Departments of Medicine and Microbiology and Immunology, Biomedical Sciences Graduate Program, and Howard Hughes Medical Institute, University of California San Francisco, 5134 Parnassus Avenue, San Francisco, CA 94143, USA
    J Biol Chem 283:15419-30. 2008
    ..Thus, we have developed the first specific chemical means of inhibiting ZAP-70 in cells, which serves as a valuable tool for studying the function of ZAP-70 in T cells...
  4. pmc Distinct roles for Syk and ZAP-70 during early thymocyte development
    Emil H Palacios
    Department of Medicine, The Rosalind Russell Medical Research Center for Arthritis, University of California San Francisco, San Francisco, CA 94143, USA
    J Exp Med 204:1703-15. 2007
    ..We propose that pre-TCR signaling continues during DN4 and later stages, with ZAP-70 dynamically replacing Syk for continued pre-TCR signaling...
  5. pmc Twisting tails exposed: the evidence for TCR conformational change
    Susan E Levin
    Rosalind Russell Medical Research Center for Arthritis, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA
    J Exp Med 201:489-92. 2005
    ..In this commentary, the evidence for TCR conformational change is reviewed and potential mechanisms for its initiation are explored...
  6. pmc The tyrosine phosphatase CD148 is excluded from the immunologic synapse and down-regulates prolonged T cell signaling
    Joseph Lin
    Department of Medicine, Biomedical Sciences Graduate Program, University of California at San Francisco, 533 Parnassus Avenue, Box no 0795, San Francisco, CA 94143 0795, USA
    J Cell Biol 162:673-82. 2003
    ..Upon T cell-APC disengagement, CD148 can then access and dephosphorylate substrates to down-regulate prolongation of signaling...
  7. pmc Phosphoinositide-dependent kinase 1 targets protein kinase A in a pathway that regulates interleukin 4
    Ajay Nirula
    Department of Medicine, The Rosalind Russell Medical Research Center for Arthritis and the Howard Hughes Medical Institute, University of California at San Francisco, CA 94143, USA
    J Exp Med 203:1733-44. 2006
    ..These findings together define a pathway linking the kinases PDK1 and PKA in the induction of the Th2 cytokine IL-4...
  8. pmc Src-like adaptor protein (SLAP) is a negative regulator of T cell receptor signaling
    T Sosinowski
    Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, California 94143 0795, USA
    J Exp Med 191:463-74. 2000
    ..These results suggest that SLAP is a negative regulator of TCR signaling...
  9. pmc Antigen receptor signaling in the rheumatic diseases
    Julie Zikherman
    Division of Rheumatology, Rosalind Russell Medical Research Center for Arthritis, Department of Medicine, Howard Hughes Medical Institute, University of California, San Francisco, 513 Parnassus Avenue San Francisco, CA 94143, USA
    Arthritis Res Ther 11:202. 2009
    ..Impaired and enhanced T-cell receptor signaling are both associated with distinct inflammatory diseases in mice. Mechanisms by which these pathways contribute to disease in mouse models and patients are under active investigation...
  10. ncbi request reprint Discovering the TCR beta-chain by subtraction
    Arthur Weiss
    Howard Hughes Medical Institute, Department of Medicine, Rosalind Russell Medical Research Center for Arthritis, University of California, San Francisco 94143, USA
    J Immunol 175:2769-70. 2005
  11. ncbi request reprint The right team at the right time to go for a home run: tyrosine kinase activation by the TCR
    Arthur Weiss
    Howard Hughes Medical Institute, Rosalind Russell Medical Research Center for Arthritis, Departments of Medicine and of Microbiology and Immunology, University of California San Francisco, San Francisco, California, USA
    Nat Immunol 11:101-4. 2010
    ..The TCR signals via cytoplasmic tyrosine kinases. Art Weiss recounts discoveries that led to early understanding of these events...
  12. pmc A genetically selective inhibitor demonstrates a function for the kinase Zap70 in regulatory T cells independent of its catalytic activity
    Byron B Au-Yeung
    Howard Hughes Medical Institute, Rosalind Russell Medical Research Center for Arthritis, Department of Medicine, Department of Microbiology and Immunology, University of California San Francisco, California, USA
    Nat Immunol 11:1085-92. 2010
    ..Our results indicate Zap70 is a likely therapeutic target...
  13. pmc T cell receptor-independent basal signaling via Erk and Abl kinases suppresses RAG gene expression
    Jeroen P Roose
    Department of Medicine, University of California, San Francisco, USA
    PLoS Biol 1:E53. 2003
    ..Our data suggest that physiologic gene expression programs depend upon tonic activity of signaling pathways independent of receptor ligation...
  14. ncbi request reprint A proline-rich motif in the C terminus of Akt contributes to its localization in the immunological synapse
    Lawrence P Kane
    Department of Medicine, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA
    J Immunol 172:5441-9. 2004
    ..Therefore, multiple mechanisms are involved in the proper targeting of Akt during the early events of T cell activation...
  15. pmc Expression and function of Tec, Itk, and Btk in lymphocytes: evidence for a unique role for Tec
    Michael G Tomlinson
    Department of Medicine and Howard Hughes Medical Institute, University of California, San Francisco, California 94143, USA
    Mol Cell Biol 24:2455-66. 2004
    ..We hypothesize that Tec functions in activated and effector T lymphocytes to induce the expression of genes regulated by NFAT transcription factors...
  16. ncbi request reprint ZAP-70 directly enhances IgM signaling in chronic lymphocytic leukemia
    Liguang Chen
    Division of Hematology Oncology, Department of Medicine, University of California, San Diego, 9500 Gilman Dr, UCSD School of Medicine, La Jolla, CA 92093, USA
    Blood 105:2036-41. 2005
    ....
  17. pmc Regulation of thymocyte positive selection and motility by GIT2
    Hyewon Phee
    Department of Medicine, University of California San Francisco, San Francisco, CA, USA
    Nat Immunol 11:503-11. 2010
    ....
  18. pmc Src-like adaptor protein (SLAP) regulates B cell receptor levels in a c-Cbl-dependent manner
    Leonard L Dragone
    Division of Pediatric Immunology Rheumatology, Department of Pediatrics, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 103:18202-7. 2006
    ..These data suggest that SLAP has a conserved function in B and T cells by adapting c-Cbl to the antigen-receptor complex and targeting it for degradation...
  19. ncbi request reprint SRC-like adaptor protein regulates B cell development and function
    Leonard L Dragone
    Division of Pediatric Immunology Rheumatology, Department of Pediatrics, University of California, San Francisco, CA 94143, USA
    J Immunol 176:335-45. 2006
    ..These data suggest that SLAP regulates BCR levels and signal strength during lymphocyte development...
  20. ncbi request reprint Dynamic recruitment of PAK1 to the immunological synapse is mediated by PIX independently of SLP-76 and Vav1
    Hyewon Phee
    Department of Medicine, Howard Hughes Medical Institute, Rosalind Russell Medical Research Center for Arthritis, University of California San Francisco, 94143, USA
    Nat Immunol 6:608-17. 2005
    ..These data indicate that a pathway involving the GIT-PIX-PAK1 complex has a crucial function in PAK1 activation by recruiting PAK1 to the immunological synapse...
  21. pmc Unusual interplay of two types of Ras activators, RasGRP and SOS, establishes sensitive and robust Ras activation in lymphocytes
    Jeroen P Roose
    Department of Medicine, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143 0795, USA
    Mol Cell Biol 27:2732-45. 2007
    ..We hypothesize that this mechanism enables lymphocytes to maximally respond to physiologically low levels of stimulation...
  22. pmc PTPN22 deficiency cooperates with the CD45 E613R allele to break tolerance on a non-autoimmune background
    Julie Zikherman
    University of California, San Francisco, 94143, USA
    J Immunol 182:4093-106. 2009
    ..These studies suggest that Pep(-/-) T cells in the context of a susceptible microenvironment can drive hyperresponsive CD45 E613R B cells to break tolerance...
  23. ncbi request reprint The juxtamembrane wedge negatively regulates CD45 function in B cells
    Michelle L Hermiston
    Department of Pediatrics, University of California, San Francisco, San Francisco, California 94143, USA
    Immunity 23:635-47. 2005
    ..Together, the results support a role for CD45 as a rheostat, with both positive and negative regulatory functions, that fine-tunes the signal transduction threshold at multiple checkpoints in B cell development...
  24. pmc A hypomorphic allele of ZAP-70 reveals a distinct thymic threshold for autoimmune disease versus autoimmune reactivity
    Lih Yun Hsu
    Department of Medicine, Rosalind Russell Medical Research Center for Arthritis, Howard Hughes Medical Institute, University of California San Francisco Children s Hospital, University of California, San Francisco, San Francisco, CA 94143, USA
    J Exp Med 206:2527-41. 2009
    ..By uncoupling the relative contribution from T regulatory cells and TCR repertoire during thymic selection, our data help to identify events that may be important, but alone are insufficient, for the development of autoimmune disease...
  25. pmc A diacylglycerol-protein kinase C-RasGRP1 pathway directs Ras activation upon antigen receptor stimulation of T cells
    Jeroen P Roose
    Department of Medicine, UCSF, 533 Parnassus Avenue, Room U 330, San Francisco, CA 94143, USA
    Mol Cell Biol 25:4426-41. 2005
    ..Conversely, active PKCtheta depends on RasGRP1 sufficiency to effectively trigger downstream events. Last, DAG-PKC-RasGRP1-driven Ras-Erk activation in T cells is a unique signaling event, not simply compensated for by SOS activity...
  26. pmc Endogenous antigen tunes the responsiveness of naive B cells but not T cells
    Julie Zikherman
    Division of Rheumatology, Department of Medicine, Rosalind Russell Medical Research Center for Arthritis, University of California, San Francisco, California 94143, USA
    Nature 489:160-4. 2012
    ..These results have important implications for understanding how tolerance in T and B cells is differently imposed, and how these processes might go awry in disease...
  27. pmc Akt-dependent phosphorylation specifically regulates Cot induction of NF-kappa B-dependent transcription
    Lawrence P Kane
    Department of Medicine The Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, California 94143, USA
    Mol Cell Biol 22:5962-74. 2002
    ..These findings suggest that the activation of different signaling pathways by MAP3Ks may be regulated separately and may provide evidence for how such discrimination by one member of this kinase family occurs...
  28. pmc Stability of an autoinhibitory interface in the structure of the tyrosine kinase ZAP-70 impacts T cell receptor response
    Sebastian Deindl
    Department of Molecular and Cell Biology, California Institute of Quantitative Biosciences, University of California, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 106:20699-704. 2009
    ..Taken together, our results directly correlate the stability of the autoinhibitory interface with the activation of these key events in the T cell response...
  29. ncbi request reprint SHIP family inositol phosphatases interact with and negatively regulate the Tec tyrosine kinase
    Michael G Tomlinson
    Department of Medicine and Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA 94143, USA
    J Biol Chem 279:55089-96. 2004
    ..These data suggest that SHIP phosphatases can interact with and functionally inactivate Tec by de-phosphorylation of local PtdIns 3,4,5-P(3) and inhibition of Tec membrane localization...
  30. ncbi request reprint Src-like adaptor protein regulates TCR expression on thymocytes by linking the ubiquitin ligase c-Cbl to the TCR complex
    Margaret D Myers
    Department of Medicine, Rosalind Russell Medical Research Center for Arthritis, Howard Hughes Medical Institute, University of California San Francisco, 94143, USA
    Nat Immunol 7:57-66. 2006
    ..These studies indicate that SLAP links the E3 ligase activity of c-Cbl to the TCR, allowing for stage-specific regulation of TCR expression...
  31. pmc Coupling Ca2+ store release to Icrac channel activation in B lymphocytes requires the activity of Lyn and Syk kinases
    S Clare Chung
    Department of Physiology, School of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
    J Cell Biol 177:317-28. 2007
    ..The action of kinases on Icrac activation does not arise from control of the expression level of the stromal interaction molecule 1 and Orai1 proteins...
  32. ncbi request reprint Structural basis for the inhibition of tyrosine kinase activity of ZAP-70
    Sebastian Deindl
    Department of Molecular and Cell Biology, Department of Chemistry, and Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA
    Cell 129:735-46. 2007
    ..These interactions are inconsistent with ITAM binding, suggesting that destabilization of this autoinhibited ZAP-70 conformation is the first step in kinase activation...
  33. pmc Structurally distinct phosphatases CD45 and CD148 both regulate B cell and macrophage immunoreceptor signaling
    Jing W Zhu
    Departments of Medicine and of Microbiology and Immunology, Howard Hughes Medical Institute, Rosalind Russell Medical Research Center for Arthritis, University of California San Francisco, San Francisco, CA 94143, USA
    Immunity 28:183-96. 2008
    ....
  34. pmc Src-like adaptor protein down-regulates T cell receptor (TCR)-CD3 expression by targeting TCRzeta for degradation
    Margaret D Myers
    Department of Medicine, Rosalind Russell Medical Research Center for Arthritis, University of California, San Francisco, CA 94143, USA
    J Cell Biol 170:285-94. 2005
    ..These studies reveal a unique mechanism by which SLAP contributes to the regulation of TCR expression during a distinct stage of thymocyte development...
  35. pmc Structural basis for activation of ZAP-70 by phosphorylation of the SH2-kinase linker
    Qingrong Yan
    Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA
    Mol Cell Biol 33:2188-201. 2013
    ..This difference is due to the ability of Tyr 319 to suppress ZAP-70 activity even when the SH2 domains are dislodged from the kinase domain, providing stringent control of ZAP-70 activity downstream of Lck...
  36. ncbi request reprint Linker for activation of T cells, zeta-associated protein-70, and Src homology 2 domain-containing leukocyte protein-76 are required for TCR-induced microtubule-organizing center polarization
    Michelle R Kuhne
    Department of Medicine, Howard Hughes Medical Institute, Rosalind Russell Center for Medical Research in Arthritis, University of California, San Francisco, CA 94143, USA
    J Immunol 171:860-6. 2003
    ..Moreover, our studies revealed that a calcium-dependent event not requiring calcineurin or calcium/calmodulin-dependent kinase is required for TCR-induced polarization of the MTOC...
  37. pmc Basal LAT-diacylglycerol-RasGRP1 signals in T cells maintain TCRα gene expression
    Evan Markegard
    Department of Anatomy, University of California San Francisco, San Francisco, California, United States of America
    PLoS ONE 6:e25540. 2011
    ..We postulate that basal LAT-diacylglycerol-RasGRP signals fulfill a regulatory function in peripheral T lymphocytes by maintaining proper gene expression programs...
  38. pmc Quantitative differences in CD45 expression unmask functions for CD45 in B-cell development, tolerance, and survival
    Julie Zikherman
    Division of Rheumatology, Department of Medicine, Rosalind Russell Medical Research Center for Arthritis and Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 109:E3-12. 2012
    ..Taken together, our findings reveal how CD45 function diverges in T cells and B cells, as well as how autoreactive B cells are censored as they transit development...
  39. pmc CD45-Csk phosphatase-kinase titration uncouples basal and inducible T cell receptor signaling during thymic development
    Julie Zikherman
    Division of Rheumatology, University of California San Francisco, San Francisco, CA 94143, USA
    Immunity 32:342-54. 2010
    ..High physiologic expression of CD45 is thus required for two reasons-to downmodulate inducible TCR signaling during positive selection and to counteract Csk during basal TCR signaling...
  40. pmc Intramolecular regulatory switch in ZAP-70: analogy with receptor tyrosine kinases
    Tomas Brdicka
    Department of Medicine, The Rosalind Russell Medical Research Center for Arthritis and Howard Hughes Medical Institute, University of California at San Francisco, 533 Parnassus Avenue, San Francisco, CA 94143 0795, USA
    Mol Cell Biol 25:4924-33. 2005
    ..Similar regulation was also noted for the related Syk kinase. These findings suggest that a general autoinhibitory mechanism employed by RTKs is also used by some cytoplasmic tyrosine kinases...
  41. pmc Dysregulation of signaling pathways in CD45-deficient NK cells leads to differentially regulated cytotoxicity and cytokine production
    David G T Hesslein
    Department of Microbiology and Immunology and Cancer Research Institute, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 103:7012-7. 2006
    ..These findings indicate that CD45-dependent regulation of ITAM-dependent signaling pathways is essential for NK cell-mediated cytokine production but not cytolytic activity...
  42. pmc Protein kinase Cδ promotes transitional B cell-negative selection and limits proximal B cell receptor signaling to enforce tolerance
    Andre Limnander
    Department of Anatomy, University of California, San Francisco, San Francisco, California, USA
    Mol Cell Biol 34:1474-85. 2014
    ..As a consequence of these distinct roles, PKCδ deficiency leads to the survival and development of a B cell repertoire that is not only aberrantly autoreactive but also hyperresponsive to antigen stimulation. ..
  43. pmc Inhibition of the kinase Csk in thymocytes reveals a requirement for actin remodeling in the initiation of full TCR signaling
    Ying Xim Tan
    Rosalind Russell Ephraim P Engleman Medical Research Center for Arthritis, Division of Rheumatology, Department of Medicine, University of California, San Francisco, California, USA
    Nat Immunol 15:186-94. 2014
    ..Thus, Csk has a critical role in preventing TCR signaling. However, our studies also revealed a requirement for actin remodeling, initiated by costimulation, for full TCR signaling. ..
  44. pmc Differential impact of the CD45 juxtamembrane wedge on central and peripheral T cell receptor responses
    Michelle L Hermiston
    Department of Pediatrics, Medicine, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 106:546-51. 2009
    ..Together, the data support a role for the CD45 wedge in regulation of T cell responses in vivo and suggest that its effects depend on cellular context...
  45. pmc ZAP-70: an essential kinase in T-cell signaling
    Haopeng Wang
    Howard Hughes Medical Institute, Rosalind Russell Medical Research Center for Arthritis, Department of Medicine, University of California, San Francisco, San Francisco, California 94143, USA
    Cold Spring Harb Perspect Biol 2:a002279. 2010
    ..Here we review the structure of ZAP-70, its regulation, its role in development and in disease. We also describe a model experimental system in which ZAP-70 function can be interrupted by a small chemical inhibitor...
  46. ncbi request reprint Regulated expression of the receptor-like tyrosine phosphatase CD148 on hemopoietic cells
    Joseph Lin
    Department of Medicine, University of California, San Francisco 94143, USA
    J Immunol 173:2324-30. 2004
    ..Together, these expression data along with previous biochemical data suggest that CD148 may play an important regulatory role to control an immune response...
  47. ncbi request reprint Distinct regions in the CD28 cytoplasmic domain are required for T helper type 2 differentiation
    Pietro G Andres
    Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California 94143, USA
    Nat Immunol 5:435-42. 2004
    ..Thus, different mechanisms underlie the induction of distinct T cell functional responses by CD28...
  48. ncbi request reprint Quantitative and temporal requirements revealed for Zap70 catalytic activity during T cell development
    Byron B Au-Yeung
    1 Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California, USA 2 Rosalind Russell Ephraim P Engleman Rheumatology Research Center, University of California, San Francisco, San Francisco, California, USA 3 Department of Medicine, University of California, San Francisco, San Francisco, California, USA 4 Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, California, USA 5
    Nat Immunol 15:687-94. 2014
    ....
  49. ncbi request reprint CD45: a critical regulator of signaling thresholds in immune cells
    Michelle L Hermiston
    Department of Pediatrics, University of California, San Francisco, 94143, USA
    Annu Rev Immunol 21:107-37. 2003
    ..Perturbation of this function may contribute to autoimmunity, immunodeficiency, and malignancy. Moreover, recent advances suggest that modulation of CD45 function can have therapeutic benefit in many disease states...
  50. pmc Feedback circuits monitor and adjust basal Lck-dependent events in T cell receptor signaling
    Jamie R Schoenborn
    Rosalind Russell Medical Research Center for Arthritis, Division of Rheumatology, Department of Medicine, University of California, San Francisco, CA 94143, USA
    Sci Signal 4:ra59. 2011
    ..Our results also suggest a role for Csk in the termination or dampening of TCR signals...
  51. ncbi request reprint ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia
    Laura Z Rassenti
    Chronic Lymphocytic Leukemia Research Consortium, University of California, San Diego, La Jolla 92093, USA
    N Engl J Med 351:893-901. 2004
    ....
  52. ncbi request reprint The PI-3 kinase/Akt pathway and T cell activation: pleiotropic pathways downstream of PIP3
    Lawrence P Kane
    Department of Medicine, The Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA
    Immunol Rev 192:7-20. 2003
    ..These pathways have been associated with TCR/CD28 costimulation, and they have also been implicated as targets of Akt...
  53. pmc Proline-rich tyrosine kinase-2 is critical for CD8 T-cell short-lived effector fate
    Soren Beinke
    Department of Medicine, Division of Rheumatology, The Howard Hughes Medical Institute, Rosalind Russell Medical Research Center for Arthritis, and Graduate Program in Biomedical Sciences, University of California, San Francisco, CA 94143 0795, USA
    Proc Natl Acad Sci U S A 107:16234-9. 2010
    ..Thus, PYK2 facilitates LFA-1-dependent CD8 T-cell responses and promotes CD8 T-cell short-lived effector fate, suggesting that PYK2 may be an interesting therapeutic target to suppress exacerbated CD8 T-cell responses...
  54. ncbi request reprint Differential expression of the ARF GAP genes GIT1 and GIT2 in mouse tissues
    Robert Schmalzigaug
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    J Histochem Cytochem 55:1039-48. 2007
    ....
  55. pmc Negative regulation of Hif1a expression and TH17 differentiation by the hypoxia-regulated microRNA miR-210
    Haopeng Wang
    1 Department of Medicine and Department of Microbiology and Immunology, the Rosalind Russell Ephraim P Engleman Medical Research Center for Arthritis, and the Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California, USA 2
    Nat Immunol 15:393-401. 2014
    ..Our study identifies miR-210 as an important regulator of T cell differentiation in hypoxia, which can limit immunopathology. ..
  56. pmc The phosphatase CD148 promotes airway hyperresponsiveness through SRC family kinases
    Tamiko R Katsumoto
    Division of Rheumatology and Rosalind Russell Medical Research Center for Arthritis, University of California San Francisco UCSF, San Francisco, California, USA
    J Clin Invest 123:2037-48. 2013
    ..Our studies identify CD148 and the SFKs it regulates in ASM as potential targets for the treatment of AHR...
  57. pmc The structural wedge domain of the receptor-like tyrosine phosphatase CD45 enforces B cell tolerance by regulating substrate specificity
    Julie Zikherman
    Division of Rheumatology, Department of Medicine, Rosalind Russell Medical Research Center for Arthritis, University of California, San Francisco, San Francisco, CA 94143, USA
    J Immunol 190:2527-35. 2013
    ..This demonstrates that relaxing negative regulation of BCR signaling, rather than enhancing positive regulation, is critical for driving autoimmunity in this system...
  58. ncbi request reprint Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation
    Emil H Palacios
    Rosalind Russell Medical Research Center for Arthritis, Department of Medicine and The Howard Hughes Medical Institute, University of California, San Francisco 94143 0795, USA
    Oncogene 23:7990-8000. 2004
    ..SFKs are required for each of these TCR-based signals, and Lck seems to be the major contributor...
  59. doi request reprint The structure, regulation, and function of ZAP-70
    Byron B Au-Yeung
    Department of Medicine, Rosalind Russell Medical Research Center for Arthritis, Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA 94143 0795, USA
    Immunol Rev 228:41-57. 2009
    ..Thus, the critical importance of ZAP-70 in TCR signaling and its predominantly T-cell-restricted expression pattern make ZAP-70 an attractive drug target for the inhibition of pathological T-cell responses in disease...
  60. ncbi request reprint Negative regulation of CD45 by differential homodimerization of the alternatively spliced isoforms
    Zheng Xu
    Department of Medicine and The Howard Hughes Medical Institute, University of California, San Francisco, CA 94143 0795, USA
    Nat Immunol 3:764-71. 2002
    ..Our results not only demonstrate the biological significance of alternative splicing in the immune system, but also suggest a model for regulating RPTP dimerization and function...
  61. pmc Receptor-like tyrosine phosphatases CD45 and CD148 have distinct functions in chemoattractant-mediated neutrophil migration and response to S. aureus
    Jing W Zhu
    Department of Medicine, Howard Hughes Medical Institute, Rosalind Russell Medical Research Center for Arthritis, University of California, San Francisco, San Francisco, CA 94143, USA
    Immunity 35:757-69. 2011
    ..Moreover, our results suggest that CD45 and CD148 preferentially target different SFK members (Hck and Fgr versus Lyn, respectively) to positively and negatively regulate GPCR pathways...
  62. ncbi request reprint The inducible expression of the tumor suppressor gene PTEN promotes apoptosis and decreases cell size by inhibiting the PI3K/Akt pathway in Jurkat T cells
    Zheng Xu
    Department of Medicine and Howard Hughes Meidcal Institute, University of California, San Francisco, California 94143 0795, USA
    Cell Growth Differ 13:285-96. 2002
    ..In summary, our results suggest that PTEN suppresses cell growth, promotes apoptosis, and decreases cell size by negatively regulating the phosphoinositide 3-kinase/Akt pathway in Jurkat T cells...
  63. pmc The ubiquitin ligase Cbl-b limits Pseudomonas aeruginosa exotoxin T-mediated virulence
    Priya Balachandran
    Program in Microbial Pathogenesis and Host Defense, University of California, San Francisco, San Francisco, California 94143, USA
    J Clin Invest 117:419-27. 2007
    ..To the best of our knowledge, this represents the first identification of a mammalian gene product that is specifically required for in vivo resistance to disease mediated by a type III-secreted effector...
  64. doi request reprint Alternative splicing of CD45: the tip of the iceberg
    Julie Zikherman
    Division of Rheumatology, Rosalind Russell Medical Research Center for Arthritis, Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA 94143, USA
    Immunity 29:839-41. 2008
    ..In this issue of Immunity, Wu et al. (2008) identify hnRNPLL as a critical regulator of both signal-induced exon skipping in CD45 and global alternative-transcript expression in memory T cells...
  65. pmc T cell receptor engagement leads to phosphorylation of clathrin heavy chain during receptor internalization
    Victoria L Crotzer
    The GW Hooper Foundation, Department of Microbiology, University of California San Francisco, 94143, USA
    J Exp Med 199:981-91. 2004
    ..Thus, we propose that CHC phosphorylation and dephosphorylation are involved in TCR internalization and that this is a regulatory mechanism linking TCR signaling to endocytosis...
  66. pmc Tyrosine kinase inhibitors reverse type 1 diabetes in nonobese diabetic mice
    Cedric Louvet
    Diabetes Center and the Department of Medicine, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 105:18895-900. 2008
    ..Thus, long-term efficacy and tolerance is likely to depend on inhibiting a combination of tyrosine kinases supporting the use of selective kinase inhibitors as a new, potentially very attractive approach for the treatment of T1D...
  67. pmc Unraveling the functional implications of GWAS: how T cell protein tyrosine phosphatase drives autoimmune disease
    Julie Zikherman
    Division of Rheumatology, Rosalind Russell Medical Research Center for Arthritis, Department of Medicine, UCSF, San Francisco, California, USA
    J Clin Invest 121:4618-21. 2011
    ..These data provide new insight as to how noncoding PTPN2 SNPs identified in GWAS could drive human autoimmune diseases...
  68. ncbi request reprint Expression of ZAP-70 is associated with increased B-cell receptor signaling in chronic lymphocytic leukemia
    Liguang Chen
    Division of Hematology Oncology, Department of Medicine, University of California, San Diego for the CLL Research Consortium, San Diego, CA, USA
    Blood 100:4609-14. 2002
    ....
  69. ncbi request reprint It's all Rel-ative: NF-kappaB and CD28 costimulation of T-cell activation
    Lawrence P Kane
    Dept of Medicine, The Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 9143 0795, USA
    Trends Immunol 23:413-20. 2002
    ..Although many questions remain, recent years have witnessed significant progress in understanding the signal transduction pathways leading from the TCR and CD28 to Rel/NF-kappaB-dependent transcription...
  70. pmc Reciprocal regulation of lymphocyte activation by tyrosine kinases and phosphatases
    Michelle L Hermiston
    Department of Pediatrics, The Howard Hughes Medical Institute, University of California, San Francisco, California 94143 0795, USA
    J Clin Invest 109:9-14. 2002
  71. ncbi request reprint Overview of the Alliance for Cellular Signaling
    Alfred G Gilman
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Nature 420:703-6. 2002
    ..One goal is to catalyse complementary research in individual laboratories; to facilitate this, all alliance data are freely available for use by the entire research community...
  72. doi request reprint The proline-rich sequence of CD3epsilon controls T cell antigen receptor expression on and signaling potency in preselection CD4+CD8+ thymocytes
    Michael Mingueneau
    Centre d immunologie de Marseille Luminy, Universite de la Mediterrannee, Case 906, Institut National de la Santé et de la Recherche Médicale U631, and Centre National de la Recherche Scientifique UMR6102, 13288 Marseille Cedex 9, France
    Nat Immunol 9:522-32. 2008
    ..Our results identify previously unknown functions for the evolutionarily conserved CD3epsilon PRS at the CD4+CD8+ developmental stage and suggest a rather limited function in mature T cells...
  73. ncbi request reprint Dynamics of p56lck translocation to the T cell immunological synapse following agonist and antagonist stimulation
    Lauren I Richie Ehrlich
    Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Immunity 17:809-22. 2002
    ..Most surprisingly, we find an intracellular pool of lck associated with recycling endosomes that translocates to mature synapses within 10 min of calcium flux. This bolus of lck may contribute to intermediate-late signal transduction...
  74. ncbi request reprint Jurkat T cells and development of the T-cell receptor signalling paradigm
    Robert T Abraham
    Program in Signal Transduction Research at The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Rev Immunol 4:301-8. 2004
  75. ncbi request reprint Synergistic assembly of linker for activation of T cells signaling protein complexes in T cell plasma membrane domains
    Lorian C Hartgroves
    Sir William Dunn School of Pathology, University of Oxford, South Parks Road, United Kingdom
    J Biol Chem 278:20389-94. 2003
    ..Taken together our data suggest a synergistic assembly of multimolecular TCR.LAT signal transduction complexes in T cell plasma membrane domains...
  76. pmc ZAP-70 enhances IgM signaling independent of its kinase activity in chronic lymphocytic leukemia
    Liguang Chen
    Moores UCSD Cancer Center, University of California San Diego, 3855 Health Sciences Drive No 0820, La Jolla, CA 92093, USA
    Blood 111:2685-92. 2008
    ..We conclude that ZAP-70 most likely acts as an adapter protein that facilitates B-cell receptor (BCR) signaling in CLL cells independent of its tyrosine kinase activity or its ability to interact with c-Cbl...