Clifford A Lowell

Summary

Affiliation: University of California
Country: USA

Publications

  1. pmc Neutrophils give us a shock
    Clifford A Lowell
    Department of Laboratory Medicine, UCSF, San Francisco, California 94143 0451, USA
    J Clin Invest 121:1260-3. 2011
  2. pmc Myeloid cells, BAFF, and IFN-gamma establish an inflammatory loop that exacerbates autoimmunity in Lyn-deficient mice
    Patrizia Scapini
    Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
    J Exp Med 207:1757-73. 2010
  3. pmc Overview: studying integrins in vivo
    Clifford A Lowell
    Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA
    Methods Mol Biol 757:369-97. 2012
  4. ncbi request reprint Transmigration of neutrophils across inflamed endothelium is signaled through LFA-1 and Src family kinase
    Melissa R Sarantos
    Department of Biomedical Engineering, University of California, Davis, CA 95616, USA
    J Immunol 181:8660-9. 2008
  5. pmc Neutrophil-specific deletion of Syk kinase results in reduced host defense to bacterial infection
    Jessica A Van Ziffle
    Immunology Program and the Department of Laboratory Medicine, University of California San Francisco, 513 Parnassus Ave, San Francisco, CA 94143 0451, USA
    Blood 114:4871-82. 2009
  6. ncbi request reprint The Src family kinases Hck and Fgr negatively regulate neutrophil and dendritic cell chemokine signaling via PIR-B
    Hong Zhang
    Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California 94143, USA
    Immunity 22:235-46. 2005
  7. pmc Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12
    Jessica A Hamerman
    Department of Microbiology and Immunology and the Cancer Research Institute, University of California San Francisco, San Francisco, California 94143, USA
    Nat Immunol 6:579-86. 2005
  8. pmc Hyperactivated MyD88 signaling in dendritic cells, through specific deletion of Lyn kinase, causes severe autoimmunity and inflammation
    Chrystelle Lamagna
    Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 110:E3311-20. 2013
  9. ncbi request reprint The inhibitory receptor PIR-B negatively regulates neutrophil and macrophage integrin signaling
    Shalini Pereira
    Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA
    J Immunol 173:5757-65. 2004
  10. pmc Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury
    Mark R Looney
    Department of Medicine, UCSF, San Francisco, California 94143 0130, USA
    J Clin Invest 119:3450-61. 2009

Detail Information

Publications79

  1. pmc Neutrophils give us a shock
    Clifford A Lowell
    Department of Laboratory Medicine, UCSF, San Francisco, California 94143 0451, USA
    J Clin Invest 121:1260-3. 2011
    ..These exciting results suggest that we have to reevaluate our models for anaphylaxis in humans, which will have a direct impact on our therapeutic approaches for prevention of this potential deadly hypersensitivity reaction...
  2. pmc Myeloid cells, BAFF, and IFN-gamma establish an inflammatory loop that exacerbates autoimmunity in Lyn-deficient mice
    Patrizia Scapini
    Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
    J Exp Med 207:1757-73. 2010
    ..Our findings uncover an important pathological role of BAFF in autoimmune disorders...
  3. pmc Overview: studying integrins in vivo
    Clifford A Lowell
    Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA
    Methods Mol Biol 757:369-97. 2012
    ....
  4. ncbi request reprint Transmigration of neutrophils across inflamed endothelium is signaled through LFA-1 and Src family kinase
    Melissa R Sarantos
    Department of Biomedical Engineering, University of California, Davis, CA 95616, USA
    J Immunol 181:8660-9. 2008
    ..We conclude that dimeric bond clusters of LFA-1/ICAM-1 provide a key outside-in signal for orienting cytoskeletal dynamics that direct PMN extravasation at sites of inflammation...
  5. pmc Neutrophil-specific deletion of Syk kinase results in reduced host defense to bacterial infection
    Jessica A Van Ziffle
    Immunology Program and the Department of Laboratory Medicine, University of California San Francisco, 513 Parnassus Ave, San Francisco, CA 94143 0451, USA
    Blood 114:4871-82. 2009
    ..These results indicate that loss of Syk kinase-mediated integrin signaling impairs leukocyte activation, leading to reduced host defense responses...
  6. ncbi request reprint The Src family kinases Hck and Fgr negatively regulate neutrophil and dendritic cell chemokine signaling via PIR-B
    Hong Zhang
    Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California 94143, USA
    Immunity 22:235-46. 2005
    ..These data support a model in which the Src family kinases Hck and Fgr function as negative regulators of myeloid cell chemokine signaling by maintaining the tonic phosphorylation of PIR-B...
  7. pmc Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12
    Jessica A Hamerman
    Department of Microbiology and Immunology and the Cancer Research Institute, University of California San Francisco, San Francisco, California 94143, USA
    Nat Immunol 6:579-86. 2005
    ..These data suggest that one or more DAP12-pairing receptors negatively regulate signaling through TLRs...
  8. pmc Hyperactivated MyD88 signaling in dendritic cells, through specific deletion of Lyn kinase, causes severe autoimmunity and inflammation
    Chrystelle Lamagna
    Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 110:E3311-20. 2013
    ..Thus, we demonstrate that hyperactivation of MyD88-dependent signaling in DCs is sufficient to drive pathogenesis of lupus-like disease, illuminating the fact that dysregulation in innate immune cells alone can lead to autoimmunity. ..
  9. ncbi request reprint The inhibitory receptor PIR-B negatively regulates neutrophil and macrophage integrin signaling
    Shalini Pereira
    Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA
    J Immunol 173:5757-65. 2004
    ..These observations point to a nonredundant role for PIR-B in the regulation of leukocyte integrin signaling...
  10. pmc Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury
    Mark R Looney
    Department of Medicine, UCSF, San Francisco, California 94143 0130, USA
    J Clin Invest 119:3450-61. 2009
    ..Furthermore, our data offer an explanation for the increased incidence of TRALI in patients with immune priming conditions, and we suggest what we believe to be a novel therapeutic approach...
  11. ncbi request reprint Role for plastin in host defense distinguishes integrin signaling from cell adhesion and spreading
    Hua Chen
    Program in Microbial Pathogenesis and Host Defense and University of California, San Francisco, San Francisco, CA 94143, USA
    Immunity 19:95-104. 2003
    ..Unlike beta2(-/-) PMN, plastin-deficient PMN adhere and spread normally. Deficiency of plastin thus separates the classical integrin receptor functions of adhesion and spreading from intracellular signal transduction...
  12. pmc Distinct roles for neutrophils and dendritic cells in inflammation and autoimmunity in motheaten mice
    Clare L Abram
    Department of Laboratory Medicine and the Program in Immunology, University of California, San Francisco 94143, USA
    Immunity 38:489-501. 2013
    ..Our data demonstrate that disruption of distinct Shp1-regulated pathways in different cell types combine to cause motheaten disease...
  13. pmc Pyk2 is required for neutrophil degranulation and host defense responses to bacterial infection
    Lynn A Kamen
    Program in Immunology, Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
    J Immunol 186:1656-65. 2011
    ..These data demonstrate the unrealized physiologic role of this kinase in regulating the adhesion-mediated release of PMN granule contents...
  14. pmc B cell-derived IL-10 suppresses inflammatory disease in Lyn-deficient mice
    Patrizia Scapini
    Department of Laboratory Medicine and Microbiology Immunology, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 108:E823-32. 2011
    ....
  15. pmc Expression of the TEL-Syk fusion protein in hematopoietic stem cells leads to rapidly fatal myelofibrosis in mice
    Michelle T Graham
    Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, United States of America
    PLoS ONE 8:e77542. 2013
    ..These data indicate that expression of TEL-Syk in fetal liver hematopoietic cells results in JAK-independent STAT5 phosphorylation ultimately leading to a uniquely aggressive and lethal form of myelofibrosis. ..
  16. pmc B cell-specific loss of Lyn kinase leads to autoimmunity
    Chrystelle Lamagna
    Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143
    J Immunol 192:919-28. 2014
    ..Our results demonstrate that B cell-intrinsic Lyn-dependent signaling pathways regulate B cell homeostasis and activation, which in concert with B cell-specific MyD88 signaling pathways can drive the development of autoimmune disease. ..
  17. ncbi request reprint The Lyn tyrosine kinase differentially regulates dendritic cell generation and maturation
    Ching Liang Chu
    Department of Laboratory Medicine, University of California, San Francisco, CA 94143 0134, USA
    J Immunol 175:2880-9. 2005
    ..This is the first study to characterize Lyn-deficient DCs. Our results suggest that Lyn kinase plays uniquely negative and positive regulatory roles in DC generation and maturation, respectively...
  18. pmc Generation of a novel system for studying spleen tyrosine kinase function in macrophages and B cells
    Allison L Miller
    Department of Laboratory Medicine, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA
    J Immunol 182:988-98. 2009
    ....
  19. ncbi request reprint G-protein-coupled receptor signaling in Syk-deficient neutrophils and mast cells
    Attila Mocsai
    Department of Laboratory Medicine, University of California, San Francisco, CA 94143 0134, USA
    Blood 101:4155-63. 2003
    ..We conclude that, in contrast to previous reports, Syk does not play a major role in GPCR signaling...
  20. pmc Deletion of Syk in neutrophils prevents immune complex arthritis
    Emily R Elliott
    Biomedical Sciences Program, University of California, San Francisco, San Francisco, CA 94143, USA
    J Immunol 187:4319-30. 2011
    ..Basophil-deficient mice also responded normally to K/BxN serum transfer. These results demonstrate that Syk-dependent signaling in neutrophils alone is critically required for arthritis development in the serum transfer model...
  21. ncbi request reprint Impaired integrin-dependent function in Wiskott-Aldrich syndrome protein-deficient murine and human neutrophils
    Hong Zhang
    Department of Laboratory Medicine, University of California, San Francisco, California 94143, USA
    Immunity 25:285-95. 2006
    ..These results suggest that impaired beta2 integrin function in WASp-deficient PMNs may contribute substantially to the clinical immunodeficiency suffered by WAS patients...
  22. pmc Multiple roles of Lyn kinase in myeloid cell signaling and function
    Patrizia Scapini
    Department of Laboratory Medicine, University of California, San Francisco, CA 94143 0451, USA
    Immunol Rev 228:23-40. 2009
    ..In this review, we discuss the current knowledge of the duplicitous nature of Lyn in the modulation of myeloid cell signaling and function...
  23. pmc The ubiquitin modifying enzyme A20 restricts B cell survival and prevents autoimmunity
    Rita M Tavares
    Department of Medicine, University of California, San Francisco, San Francisco, CA, USA
    Immunity 33:181-91. 2010
    ..These findings show that A20 can restrict B cell survival, whereas A20 protects other cells from TNF-induced cell death. Our studies demonstrate how reduced A20 expression predisposes to autoimmunity...
  24. 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...
  25. ncbi request reprint The expanding role for ITAM-based signaling pathways in immune cells
    Clare L Abram
    Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA
    Sci STKE 2007:re2. 2007
    ....
  26. pmc Neutrophils and their Fc gamma receptors are essential in a mouse model of transfusion-related acute lung injury
    Mark R Looney
    Cardiovascular Research Institute, Department of Medicine, UCSF, San Francisco, California, USA
    J Clin Invest 116:1615-23. 2006
    ..In conclusion, in a clinically relevant in vivo mouse model of TRALI using an MHC I mAb, the mechanism of lung injury was dependent on neutrophils and their Fc gamma receptors...
  27. pmc The immunomodulatory adapter proteins DAP12 and Fc receptor gamma-chain (FcRgamma) regulate development of functional osteoclasts through the Syk tyrosine kinase
    Attila Mocsai
    Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 101:6158-63. 2004
    ..These results provide new insight into the biology of osteoclasts and suggest novel therapeutic targets in diseases of bony remodeling...
  28. pmc Transfusion-related acute lung injury: incidence and risk factors
    Pearl Toy
    Department of Laboratory Medicine, Box 0451, University of California San Francisco, San Francisco, CA 94143 0451, USA
    Blood 119:1757-67. 2012
    ..57 (95% CI, 1.72-3.86) in 2006 versus 0.81 (95% CI, 0.44-1.49) in 2009 per 10 000 transfused units (P = .002). The identified risk factors provide potential targets for reducing residual TRALI...
  29. pmc Strain-dependent induction of neutrophil histamine production and cell death by Pseudomonas aeruginosa
    Xiang Xu
    Department of Medicine, University of California at San Francisco, San Francisco, California, USA
    J Leukoc Biol 91:275-84. 2012
    ..These findings raise the possibility that Pseudomonas-stimulated neutrophils can enhance airway inflammation by producing histamine...
  30. ncbi request reprint Convergence of immunoreceptor and integrin signaling
    Clare L Abram
    Department of Laboratory Medicine, University of California, San Francisco, CA 94143 0451, USA
    Immunol Rev 218:29-44. 2007
    ..In this review, we discuss the convergence of immunoreceptor and integrin signaling, focusing on how these pathways modulate leukocyte activation...
  31. ncbi request reprint Prospective study on the clinical course and outcomes in transfusion-related acute lung injury*
    Mark R Looney
    1Department of Medicine, University of California San Francisco, San Francisco, CA 2Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA 3Blood Systems Research Institute, San Francisco, CA 4Department of Medicine, Mayo Clinic, Rochester, MN 5Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA 6Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA 7Department of Anesthesia, Mayo Clinic, Rochester, MN 8Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 9American Red Cross Neutrophil Reference Laboratory, St Paul, MN 10Blood Centers of the Pacific, San Francisco, CA
    Crit Care Med 42:1676-87. 2014
    ..A prospective study using electronic surveillance was conducted at two academic medical centers in the United States with the objective to define the clinical course and outcomes in transfusion-related acute lung injury cases...
  32. pmc The ins and outs of leukocyte integrin signaling
    Clare L Abram
    Program in Immunology, Department of Laboratory Medicine, University of California, San Francisco, California 94143 0451, USA
    Annu Rev Immunol 27:339-62. 2009
    ....
  33. ncbi request reprint Comparative analysis of the efficiency and specificity of myeloid-Cre deleting strains using ROSA-EYFP reporter mice
    Clare L Abram
    Department of Laboratory Medicine and the Program in Immunology, University of California, San Francisco, CA 94143, USA
    J Immunol Methods 408:89-100. 2014
    ..By focusing on myeloid subsets, we directly compare the relative efficiency and specificity of myeloid deletion in these strains under steady-state conditions. ..
  34. ncbi request reprint Src-family kinases: rheostats of immune cell signaling
    Clifford A Lowell
    Department of Laboratory Medicine, University of California, San Francisco, 505 Parnassus Avenue HSE590, San Francisco, CA 94143 0100, USA
    Mol Immunol 41:631-43. 2004
    ..The overall observation that these molecules play such diverse signaling functions leads one to the conclusion that this family of proteins serves as general modulators of immune cell signaling...
  35. pmc Complement activation and intraventricular rituximab distribution in recurrent central nervous system lymphoma
    Cigall Kadoch
    Authors Affiliations Division of Hematology Oncology, Genentech, South San Francisco Helen Diller Comprehensive Cancer Center and Department of Radiology, Laboratory Medicine, University of California, San Francisco, San Francisco, California
    Clin Cancer Res 20:1029-41. 2014
    ..To elucidate the mechanistic basis for efficacy of intrathecal rituximab. We evaluated complement activation as well as the pharmacokinetics of intraventricular rituximab in patients who participated in two phase 1 multicenter studies...
  36. ncbi request reprint The diverse functions of Src family kinases in macrophages
    Clare L Abram
    Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA
    Front Biosci 13:4426-50. 2008
    ..In general, SFKs may function more like rheostats, influencing the amplitude of many pathways...
  37. ncbi request reprint Syk is required for integrin signaling in neutrophils
    Attila Mocsai
    Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA
    Immunity 16:547-58. 2002
    ..Thus, integrins use different signaling mechanisms to support migration and adherent activation...
  38. doi request reprint Pathologic correlates of primary central nervous system lymphoma defined in an orthotopic xenograft model
    Cigall Kadoch
    Division of Hematology Oncology, Department of Neurological Surgery, University of California at San Francisco, San Francisco, California, USA
    Clin Cancer Res 15:1989-97. 2009
    ..Animal models of PCNSL are needed to facilitate the analysis of its molecular pathogenesis and for the efficient evaluation of novel therapeutics...
  39. pmc Fresh and stored red blood cell transfusion equivalently induce subclinical pulmonary gas exchange deficit in normal humans
    Richard B Weiskopf
    Department of Anesthesia and Perioperative Care, University of California, San Francisco, Box 0648, San Francisco, CA 94143 0648, USA
    Anesth Analg 114:511-9. 2012
    ..We tested the hypothesis that transfusion can cause mild pulmonary dysfunction that has not been noticed clinically and is not sufficiently severe to fit the definition of transfusion-related acute lung injury...
  40. pmc Differential transformation capacity of Src family kinases during the initiation of prostate cancer
    Houjian Cai
    Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
    Proc Natl Acad Sci U S A 108:6579-84. 2011
    ..Our data indicate that development of inhibitors against specific SFK members could provide unique targeted therapeutic strategies...
  41. ncbi request reprint Rewiring phagocytic signal transduction
    Clifford A Lowell
    Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California 94143, USA
    Immunity 24:243-5. 2006
    ..In this issue of Immunity, primary macrophages from Vav1(-/-)/Vav3(-/-) and Rac1(-/-)/Rac2(-/-) mice to produce a new picture of Fcgamma receptor and complement receptor 3 intracellular signaling have been examined...
  42. pmc Regulation of myeloproliferation and M2 macrophage programming in mice by Lyn/Hck, SHIP, and Stat5
    Wenbin Xiao
    Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA
    J Clin Invest 118:924-34. 2008
    ..Thus, this study has defined a myeloproliferative transformation-sensitive signaling pathway, composed of Lyn/Hck, SHIP, autocrine/paracrine cytokines, and Stat5, that regulates HSC differentiation and M2 macrophage programming...
  43. pmc Increased TLR responses in dendritic cells lacking the ITAM-containing adapters DAP12 and FcRgamma
    Ching Liang Chu
    Immunology Research Center, National Health Research Institutes, Taiwan
    Eur J Immunol 38:166-73. 2008
    ....
  44. pmc Myeloid Src kinases regulate phagocytosis and oxidative burst in pneumococcal meningitis by activating NADPH oxidase
    Robert Paul
    Department of Neurology, Klinikum Grosshadern, Ludwig Maximilians University, Marchioninistr 15, D 81377 Munich, Germany
    J Leukoc Biol 84:1141-50. 2008
    ..These data support the role of SFKs as critical mediators of CR3 signal transduction in host defense...
  45. pmc PSGL-1 engagement by E-selectin signals through Src kinase Fgr and ITAM adapters DAP12 and FcR gamma to induce slow leukocyte rolling
    Alexander Zarbock
    Robert M Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA
    J Exp Med 205:2339-47. 2008
    ....
  46. pmc Src family tyrosine kinase Lyn mediates VWF/GPIb-IX-induced platelet activation via the cGMP signaling pathway
    Hong Yin
    Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612, USA
    Blood 112:1139-46. 2008
    ....
  47. pmc G-CSF induced reactive oxygen species involves Lyn-PI3-kinase-Akt and contributes to myeloid cell growth
    Quan Sheng Zhu
    Division of Pediatrics, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Blood 107:1847-56. 2006
    ..These data suggest that the G-CSF-induced Lyn-PI3K-Akt pathway drives ROS production. One beneficial effect of therapeutic targeting of Lyn-PI3K-kinase-Akt cascade is abrogating ROS production...
  48. ncbi request reprint SLP-76 regulates Fcgamma receptor and integrin signaling in neutrophils
    Sally A Newbrough
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Immunity 19:761-9. 2003
    ..These results provide genetic evidence for a critical role of SLP-76 in the regulation of neutrophil function...
  49. pmc Src-family kinases mediate an outside-in signal necessary for beta2 integrins to achieve full activation and sustain firm adhesion of polymorphonuclear leucocytes tethered on E-selectin
    Licia Totani
    Laboratory of Vascular Biology and Pharmacology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Italy
    Biochem J 396:89-98. 2006
    ..Thus, Src-family kinases, and perhaps Pyk2, mediate a signal necessary for beta2 integrin function in PMN tethered by E-selectin...
  50. pmc Src family kinases are important negative regulators of G-CSF-dependent granulopoiesis
    Craig H Mermel
    Division of Oncology, Department of Medicine, Washington University School of Medicine, 660 S Euclid Ave, Campus Box 8007, Saint Louis, MO 63110, USA
    Blood 108:2562-8. 2006
    ..Together, these data establish Lyn and Hck as key negative regulators of granulopoiesis and raise the possibility that loss of Src family kinase activation by the d715 G-CSFR may contribute to its hyperproliferative phenotype...
  51. ncbi request reprint Integrin signaling in neutrophils and macrophages uses adaptors containing immunoreceptor tyrosine-based activation motifs
    Attila Mocsai
    Department of Physiology, Semmelweis University School of Medicine, 1088 Budapest, Hungary
    Nat Immunol 7:1326-33. 2006
    ..Our data show that integrin signaling for the activation of cellular responses in neutrophils and macrophages proceeds by an immunoreceptor-like mechanism...
  52. pmc Src family kinases mediate neutrophil adhesion to adherent platelets
    Virgilio Evangelista
    Laboratory of Vascular Biology and Pharmacology, Consorzio Mario Negri Sud, Via Nazionale 8 A, 66030 Santa Maria Imbaro, Italy
    Blood 109:2461-9. 2007
    ..These results definitely establish a role for SFKs in PMN recruitment by activated platelets and suggest novel targets to disrupt the pathophysiologic consequences of platelet-leukocyte interactions in vascular disease...
  53. pmc Neutrophil histamine contributes to inflammation in mycoplasma pneumonia
    Xiang Xu
    Cardiovascular Research Institute, Department of Microbiology Immunology, University of California at San Francisco, and Veterans Affairs Medical Center, San Francisco 94121, USA
    J Exp Med 203:2907-17. 2006
    ..These findings suggest that neutrophils, provoked by mycoplasma, greatly expand their capacity to synthesize histamine, thereby contributing to lung and airway inflammation...
  54. ncbi request reprint The Src family kinases Hck and Fgr regulate neutrophil responses to N-formyl-methionyl-leucyl-phenylalanine
    Laura Fumagalli
    Department of Pathology, Section of General Pathology, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy
    J Immunol 178:3874-85. 2007
    ..We suggest that Hck and Fgr act within a signaling pathway triggered by fMLP receptors that involves Vav1 and p21-activated kinases, leading to respiratory burst and F-actin polymerization...
  55. ncbi request reprint Src and Syk kinases: key regulators of phagocytic cell activation
    Giorgio Berton
    Department of Pathology, Section of General Pathology, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy
    Trends Immunol 26:208-14. 2005
    ..Elucidating the regulation of these tyrosine kinase-based signaling pathways in leukocytes remains an important goal in understanding how immune cells respond to the multitude of activating agents they encounter...
  56. ncbi request reprint Responses of neutrophils to anti-integrin antibodies depends on costimulation through low affinity Fc gamma Rs: full activation requires both integrin and nonintegrin signals
    Zoltan Jakus
    Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary
    J Immunol 173:2068-77. 2004
    ..g., through TNF or FcR ligation) is indispensable for full integrin-mediated activation of neutrophils. These second signals are interchangeable and they may converge on the p38 MAPK...
  57. ncbi request reprint Fgr deficiency results in defective eosinophil recruitment to the lung during allergic airway inflammation
    Lucia Vicentini
    Department of Pathology, Section of General Pathology, University of Verona, Italy
    J Immunol 168:6446-54. 2002
    ..These results identify Fgr as a novel pharmacological target to control allergic inflammation...
  58. ncbi request reprint The Src kinase Lyn is a negative regulator of mast cell proliferation
    Valerie Hernandez-Hansen
    Department of Pathology and Cancer Research and Treatment Center, University of New Mexico School of Medicine, CRF Rm 205, 2325 Camino de Salud NE, Albuquerque, NM 87131, USA
    J Leukoc Biol 75:143-51. 2004
    ..These results identify Lyn as a negative regulator of murine MC survival and proliferation...
  59. pmc Neutrophil protein kinase Cdelta as a mediator of stroke-reperfusion injury
    Wen Hai Chou
    Ernest Gallo Clinic and Research Center at the University of California San Francisco, Emeryville, California 94608, USA
    J Clin Invest 114:49-56. 2004
    ..These results indicate an important role for neutrophil PKCdelta in reperfusion injury and strongly suggest that PKCdelta inhibitors could prove useful in the treatment of stroke...
  60. ncbi request reprint Immunoreceptor-like signaling by beta 2 and beta 3 integrins
    Zoltan Jakus
    Department of Physiology, Semmelweis University School of Medicine, 1088 Budapest, Hungary
    Trends Cell Biol 17:493-501. 2007
    ..These and other reports reveal an unexpected similarity between the signal-transduction mechanisms used by integrins and immune recognition receptors...
  61. ncbi request reprint Dysregulated FcepsilonRI signaling and altered Fyn and SHIP activities in Lyn-deficient mast cells
    Valerie Hernandez-Hansen
    Department of Pathology and Cancer Research and Treatment Center, University of New Mexico School of Medicine, CRF 205, 2325 Camino de Salud, Albuquerque, NM 87131, USA
    J Immunol 173:100-12. 2004
    ..The unexpected absence of the transient receptor potential channel, Trpc4, from Lyn(-/-) BMMCs may additionally contribute to their altered signaling properties...
  62. pmc Evidence that IgE molecules mediate a spectrum of effects on mast cell survival and activation via aggregation of the FcepsilonRI
    Jiro Kitaura
    Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA
    Proc Natl Acad Sci U S A 100:12911-6. 2003
    ..In hybridoma-transplanted mice, mucosal mast cell numbers correlate with serum IgE levels. Therefore, survival effects of IgE could contribute to the pathogenesis of allergic disease...
  63. ncbi request reprint Reduced dosage of Bruton's tyrosine kinase uncouples B cell hyperresponsiveness from autoimmunity in lyn-/- mice
    Lindsey R Whyburn
    Harold Simmons Arthritis Research Center, Department of Internal Medicine and Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    J Immunol 171:1850-8. 2003
    ..Thus, B cell hyperresponsiveness is insufficient for autoimmunity in lyn(-/-) mice. These studies implicate B-1 and/or myeloid cells as key contributors to the lyn(-/-) autoimmune phenotype...
  64. ncbi request reprint Expression and tyrosine phosphorylation of Cbl regulates macrophage chemokinetic and chemotactic movement
    Elena Caveggion
    Department of Pathology, Section of General Pathology, University of Verona, Verona, Italy
    J Cell Physiol 195:276-89. 2003
    ..As Hck and Fgr expression and activity were not decreased in c-cbl(-/-) macrophages, these results suggest that Cbl is likely to be an important downstream mediator of the Src family kinase-regulated macrophage motility pathway...
  65. ncbi request reprint Essential role of Src-family protein tyrosine kinases in NF-kappaB activation during B cell development
    Kaoru Saijo
    Laboratory of Lymphocyte Signaling, The Rockefeller University, New York, NY 10021, USA
    Nat Immunol 4:274-9. 2003
    ..Our data show the existence of a functionally distinct SFK signaling module responsible for pre-BCR-mediated NF-kappaB activation and B cell development...
  66. ncbi request reprint Early divergence of Fc epsilon receptor I signals for receptor up-regulation and internalization from degranulation, cytokine production, and survival
    Jiro Kitaura
    Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA
    J Immunol 173:4317-23. 2004
    ..Collectively, signals emanated from IgE-bound FcepsilonRI for receptor up-regulation and internalization are shown to diverge at the receptor or receptor-proximal levels from those for other biological outcomes...
  67. ncbi request reprint Role of the Src family kinase Lyn in TxA2 production, adenosine diphosphate secretion, Akt phosphorylation, and irreversible aggregation in platelets stimulated with gamma-thrombin
    Moon J Cho
    Department of Microbiology and Molecular Cell Sciences, University of Memphis, Memphis, TN 38152, USA
    Blood 99:2442-7. 2002
    ..Specifically, Lyn is required under these conditions to enable thrombin-induced TxA2 production and adenosine diphosphate secretion, necessary steps in secretion-dependent platelet aggregation...
  68. ncbi request reprint The proto-oncogene Fgr regulates cell migration and this requires its plasma membrane localization
    Silvia Continolo
    Department of Pathology, Section of General Pathology, University of Verona, Verona, Italy
    Exp Cell Res 302:253-69. 2005
    ..These findings suggest that the proto-oncogene Fgr regulates cell migration impinging on a signaling pathway implicating FAK/Pyk2 and leading to activation of Rac and the Rho inhibitor p190RhoGAP...
  69. pmc Spleen tyrosine kinase Syk is necessary for E-selectin-induced alpha(L)beta(2) integrin-mediated rolling on intercellular adhesion molecule-1
    Alexander Zarbock
    Robert M Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA
    Immunity 26:773-83. 2007
    ..This identifies a second neutrophil-activation pathway that is as important as activation through G protein-coupled receptors (GPCRs)...
  70. pmc The Src family kinase Hck regulates mast cell activation by suppressing an inhibitory Src family kinase Lyn
    Hong Hong
    Division of Cell Biology, La Jolla Institute for Allergy and Immunology, CA 92037, USA
    Blood 110:2511-9. 2007
    ..Thus, this study has revealed a hierarchical regulation among SFK members to fine-tune mast cell activation...
  71. ncbi request reprint Cutting Edge: B cell receptor (BCR) cross-talk: the IL-4-induced alternate pathway for BCR signaling operates in parallel with the classical pathway, is sensitive to Rottlerin, and depends on Lyn
    Benchang Guo
    Center for Oncology and Cell Biology, Feinstein Institute for Medical Research, Manhasset, NY 11030, USA
    J Immunol 178:4726-30. 2007
    ..These results indicate that the rottlerin-sensitive, Lyn-dependent alternate pathway, and the classical pathway, for BCR signaling operate in parallel when BCR engagement follows IL-4 exposure...
  72. pmc Lyn kinase promotes erythroblast expansion and late-stage development
    Vinit G Karur
    Maine Medical Center Research Institute, 81 Research Dr, Scarborough, ME 04074, USA
    Blood 108:1524-32. 2006
    ..Lyn, therefore, is proposed to function via erythroid cell-intrinsic mechanisms to promote progenitor cell expansion beyond a Kit(pos)CD71(high) stage and to support subsequent late-stage development...
  73. ncbi request reprint Dual function for the adaptor MIST in IFN-gamma production by NK and CD4+NKT cells regulated by the Src kinase Fgr
    Hiroki Sasanuma
    Division of Molecular Biology, Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba 278 0022, Japan
    Blood 107:3647-55. 2006
    ..This functional interdependence of signaling molecules demonstrates a new mechanism by which adaptor proteins can act as molecular switches to control diverse responses in different cell populations...
  74. ncbi request reprint Increased expression of genes linked to FcepsilonRI Signaling and to cytokine and chemokine production in Lyn-deficient mast cells
    Valerie Hernandez-Hansen
    Department of Pathology and Cancer Research and Treatment Center, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA
    J Immunol 175:7880-8. 2005
    ..These microarray data identify Lyn as a negative regulator in Ag-stimulated BMMCs of the expression of genes linked to FcepsilonRI signaling and also to the response pathways that lead to allergy and asthma...
  75. pmc Positive and negative regulation of mast cell activation by Lyn via the FcepsilonRI
    Wenbin Xiao
    Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA
    J Immunol 175:6885-92. 2005
    ..Furthermore, Lyn-mediated negative regulation was shown to be exerted via the FcepsilonRI beta-ITAM...
  76. ncbi request reprint The regulation of the expression of inducible nitric oxide synthase by Src-family tyrosine kinases mediated through MyD88-independent signaling pathways of Toll-like receptor 4
    Joo Y Lee
    Department of Nutrition, University of California Davis, ARS, Western Human Nutrition Research Center, Meyer Hall, 95616, USA
    Biochem Pharmacol 70:1231-40. 2005
    ..These results provide new insight in understanding the role of STKs in TLR4 signaling pathways and inflammatory target gene expression...
  77. ncbi request reprint Regulation of highly cytokinergic IgE-induced mast cell adhesion by Src, Syk, Tec, and protein kinase C family kinases
    Jiro Kitaura
    Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA
    J Immunol 174:4495-504. 2005
    ..Thus, binding of HC IgEs to Fc epsilon RI induces adhesion of mast cells to fibronectin by modulating cellular activation signals in a unique fashion...
  78. pmc IgE- and IgE+Ag-mediated mast cell migration in an autocrine/paracrine fashion
    Jiro Kitaura
    Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 10 355 Science Center Dr, San Diego, CA 92121, USA
    Blood 105:3222-9. 2005
    ..In mouse experiments, naive mast cells are attracted to IgE, and IgE-sensitized mast cells are attracted to antigen. Therefore, IgE and antigen are implicated in mast cell accumulation at allergic tissue sites with local high IgE levels...
  79. pmc Coordinate interactions of Csk, Src, and Syk kinases with [alpha]IIb[beta]3 initiate integrin signaling to the cytoskeleton
    Achim Obergfell
    Division of Vascular Biology, Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Cell Biol 157:265-75. 2002
    ..These studies establish that platelet spreading on fibrinogen requires sequential activation of Src and Syk in proximity to alphaIIbbeta3, thus providing a paradigm for initiation of integrin signaling to the actin cytoskeleton...

Research Grants16

  1. Signaling by Cytoplasmic Tyrosine Kinases in Leukocytes
    Clifford Lowell; Fiscal Year: 2002
    ..abstract_text> ..
  2. Signaling by Cytoplasmic Tyrosine Kinases in Leukocytes
    Clifford Lowell; Fiscal Year: 2009
    ..These studies will better define the roles of Src-family and Syk kinases in innate immune function, contributing significantly to our mechanistic understanding of immune response in biodefense in emerging infectious disease. ..
  3. Mechanisms of Leukocyte Integrin Signaling
    Clifford Lowell; Fiscal Year: 2005
    ..Therapeutic targeting of the integrin outside-in signaling pathway may provide novel classes of anti-inflammatory drugs. ..
  4. Signaling by Cytoplasmic Tyrosine Kinases in Leukocytes
    Clifford Lowell; Fiscal Year: 2006
    ..These studies will better define the roles of Src-family and Syk kinases in innate immune function, contributing significantly to our mechanistic understanding of immune response in biodefense in emerging infectious disease. ..
  5. Signaling by Cytoplasmic Tyrosine Kinases in Leukocytes
    Clifford Lowell; Fiscal Year: 2001
    ..abstract_text> ..
  6. FASEB Summer Conference on Signal Transduction in the Immune System
    Clifford Lowell; Fiscal Year: 2007
    ..Thus, it is hoped that this conference will build upon past conferences influencing the direction of this research and facilitating the pace of discovery. ..
  7. Signaling by Cytoplasmic Tyrosine Kinases in Leukocytes
    Clifford Lowell; Fiscal Year: 2007
    ..These studies will better define the roles of Src-family and Syk kinases in innate immune function, contributing significantly to our mechanistic understanding of immune response in biodefense in emerging infectious disease. ..
  8. Mechanisms of Leukocyte Integrin Signaling
    Clifford Lowell; Fiscal Year: 2006
    ..Therapeutic targeting of the integrin outside-in signaling pathway may provide novel classes of anti-inflammatory drugs. ..
  9. Signaling by Cytoplasmic Tyrosine Kinases in Leukocytes
    Clifford Lowell; Fiscal Year: 2005
    ..abstract_text> ..
  10. Signaling by Cytoplasmic Tyrosine Kinases in Leukocytes
    Clifford Lowell; Fiscal Year: 2004
    ..abstract_text> ..
  11. Signaling by Cytoplasmic Tyrosine Kinases in Leukocytes
    Clifford Lowell; Fiscal Year: 2003
    ..abstract_text> ..
  12. Mechanisms of Leukocyte Integrin Signaling
    Clifford Lowell; Fiscal Year: 2007
    ..Therapeutic targeting of the integrin outside-in signaling pathway may provide novel classes of anti-inflammatory drugs. ..
  13. Mechanisms of Leukocyte Integrin Signaling
    Clifford Lowell; Fiscal Year: 2009
    ..Therapeutic targeting of the integrin outside-in signaling pathway may provide novel classes of anti-inflammatory drugs. ..
  14. Signaling by Cytoplasmic Tyrosine Kinases in Leukocytes
    Clifford A Lowell; Fiscal Year: 2010
    ..These studies will better define the roles of Src-family and Syk kinases in innate immune function, contributing significantly to our mechanistic understanding of immune response in biodefense in emerging infectious disease. ..