Michael A Beaven

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. pmc Our perception of the mast cell from Paul Ehrlich to now
    Michael A Beaven
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Eur J Immunol 39:11-25. 2009
  2. ncbi request reprint Division of labor: specialization of sphingosine kinases in mast cells
    Michael A Beaven
    National Heart, Lung, and Blood Institute, National Institutes of Health, Room 8N109 Bldg 10, Bethesda, MD 20892, USA
    Immunity 26:271-3. 2007
  3. pmc Activation of RBL-2H3 mast cells is dependent on tyrosine phosphorylation of phospholipase D2 by Fyn and Fgr
    Wahn Soo Choi
    Laboratory of Molecular Immunology, National, Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA
    Mol Cell Biol 24:6980-92. 2004
  4. pmc A novel KIT-deficient mouse mast cell model for the examination of human KIT-mediated activation responses
    Daniel Smrz
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, MSC 1881, Bethesda, MD 20892 1881, USA
    J Immunol Methods 390:52-62. 2013
  5. pmc The phosphoinositide 3-kinase-dependent activation of Btk is required for optimal eicosanoid production and generation of reactive oxygen species in antigen-stimulated mast cells
    Hye Sun Kuehn
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 181:7706-12. 2008
  6. pmc Phospholipase d promotes lipid microdomain-associated signaling events in mast cells
    Felipe A Lisboa
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1760, USA
    J Immunol 183:5104-12. 2009
  7. ncbi request reprint Kit and FcepsilonRI mediate unique and convergent signals for release of inflammatory mediators from human mast cells
    Thomas R Hundley
    National Institutes of Health, Bethesda, MD 20892 1760, USA
    Blood 104:2410-7. 2004
  8. ncbi request reprint Btk plays a crucial role in the amplification of Fc epsilonRI-mediated mast cell activation by kit
    Shoko Iwaki
    Laboratory of Allergic Diseases, NIAID, National Institutes of Health, Bethesda, Maryland 20892 1881, USA
    J Biol Chem 280:40261-70. 2005
  9. pmc Synergistic activation of phospholipases Cgamma and Cbeta: a novel mechanism for PI3K-independent enhancement of FcepsilonRI-induced mast cell mediator release
    Hye Sun Kuehn
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive MSC 1881, Bethesda, MD 20892 1881, USA
    Cell Signal 20:625-36. 2008
  10. pmc IL-33 induces a hyporesponsive phenotype in human and mouse mast cells
    Mi Yeon Jung
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 190:531-8. 2013

Collaborators

Detail Information

Publications41

  1. pmc Our perception of the mast cell from Paul Ehrlich to now
    Michael A Beaven
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Eur J Immunol 39:11-25. 2009
    ..This once enigmatic cell of Paul Ehrlich has proved to be both adaptable and multifunctional...
  2. ncbi request reprint Division of labor: specialization of sphingosine kinases in mast cells
    Michael A Beaven
    National Heart, Lung, and Blood Institute, National Institutes of Health, Room 8N109 Bldg 10, Bethesda, MD 20892, USA
    Immunity 26:271-3. 2007
    ..Olivera et al. (2007) show that SphK2 regulates mast cell activation whereas SphK1 enhances susceptibility to antigen challenge in vivo...
  3. pmc Activation of RBL-2H3 mast cells is dependent on tyrosine phosphorylation of phospholipase D2 by Fyn and Fgr
    Wahn Soo Choi
    Laboratory of Molecular Immunology, National, Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA
    Mol Cell Biol 24:6980-92. 2004
    ..The findings provide the first description of a mechanism for activation of PLD2 in a physiological setting and of a role for Fgr in Fc epsilon RI-mediated signaling...
  4. pmc A novel KIT-deficient mouse mast cell model for the examination of human KIT-mediated activation responses
    Daniel Smrz
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, MSC 1881, Bethesda, MD 20892 1881, USA
    J Immunol Methods 390:52-62. 2013
    ..This cell line thus presents a novel system to delineate how MC function is modulated by native and mutated KIT and for the identification of novel inhibitors of these processes...
  5. pmc The phosphoinositide 3-kinase-dependent activation of Btk is required for optimal eicosanoid production and generation of reactive oxygen species in antigen-stimulated mast cells
    Hye Sun Kuehn
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 181:7706-12. 2008
    ..These data demonstrate that strategies to decrease mast cell production of ROS and eicosanoids would have to target both ERK1/2- and PI3K/Btk-dependent pathways...
  6. pmc Phospholipase d promotes lipid microdomain-associated signaling events in mast cells
    Felipe A Lisboa
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1760, USA
    J Immunol 183:5104-12. 2009
    ..Collectively, these findings suggest that PLD activity plays an important role in promoting IgE-dependent signaling events within lipid microdomains in mast cells...
  7. ncbi request reprint Kit and FcepsilonRI mediate unique and convergent signals for release of inflammatory mediators from human mast cells
    Thomas R Hundley
    National Institutes of Health, Bethesda, MD 20892 1760, USA
    Blood 104:2410-7. 2004
    ..The findings, in total, indicated that a combination of FcepsilonRI and Kit-mediated signals and transcriptional processes were required for optimal physiologic responses of human mast cells to antigen...
  8. ncbi request reprint Btk plays a crucial role in the amplification of Fc epsilonRI-mediated mast cell activation by kit
    Shoko Iwaki
    Laboratory of Allergic Diseases, NIAID, National Institutes of Health, Bethesda, Maryland 20892 1881, USA
    J Biol Chem 280:40261-70. 2005
    ..These data demonstrate, for the first time, that Btk is a key regulator of a Kit-mediated amplification pathway that augments Fc epsilonRI-mediated mast cell activation...
  9. pmc Synergistic activation of phospholipases Cgamma and Cbeta: a novel mechanism for PI3K-independent enhancement of FcepsilonRI-induced mast cell mediator release
    Hye Sun Kuehn
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive MSC 1881, Bethesda, MD 20892 1881, USA
    Cell Signal 20:625-36. 2008
    ..These responses were critical for the promotion of degranulation. This is the first report of synergistic activation between PLCgamma and PLCbeta that permits reinforcement of signals for degranulation in mast cells...
  10. pmc IL-33 induces a hyporesponsive phenotype in human and mouse mast cells
    Mi Yeon Jung
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 190:531-8. 2013
    ..The ability to downregulate MC activation in this manner may provide alternative approaches for treatment of MC-driven disease...
  11. pmc Stem cell factor programs the mast cell activation phenotype
    Tomonobu Ito
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 188:5428-37. 2012
    ....
  12. ncbi request reprint An essential role for phospholipase D in the activation of protein kinase C and degranulation in mast cells
    Ze Peng
    Laboratory of Molecular Immunology, National, Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA
    J Immunol 174:5201-8. 2005
    ..These results suggested that the production of phosphatidic acid by PLD facilitates activation of PKC and, in turn, degranulation, although additional PLD-dependent processes appear to be critical for Ag-mediated degranulation...
  13. pmc FcepsilonR1 and toll-like receptors mediate synergistic signals to markedly augment production of inflammatory cytokines in murine mast cells
    Huihong Qiao
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1760, USA
    Blood 107:610-8. 2006
    ..The synergistic interactions of TLR ligands and antigen might have relevance to the exacerbation of IgE-mediated allergic diseases by infectious agents...
  14. pmc Canonical transient receptor potential 5 channel in conjunction with Orai1 and STIM1 allows Sr2+ entry, optimal influx of Ca2+, and degranulation in a rat mast cell line
    Hong Tao Ma
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 180:2233-9. 2008
    ..These and other observations suggest that the Sr(2+)-permeable TRPC5 associates with STIM1 and Orai1 in a stoichiometric manner to enhance entry of Ca(2+) to generate a signal for degranulation...
  15. pmc Src-like adaptor protein (SLAP) is upregulated in antigen-stimulated mast cells and acts as a negative regulator
    Seung Kiel Park
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Immunol 46:2133-9. 2009
    ..Production of IL-3 and MCP-1, but not degranulation, is also enhanced. The upregulation of SLAP may thus serve to limit the duration of cytokine production in Ag-stimulated cells...
  16. ncbi request reprint Serine/threonine protein kinases synergistically regulate phospholipase D1 and 2 and secretion in RBL-2H3 mast cells
    Ahmed Chahdi
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institute of Health, Bethesda, MD 20892 1760, USA
    Mol Immunol 38:1269-76. 2002
    ..As the expressed PLD1 was associated with secretory granules and PLD2 with the plasma membrane, the two isoforms may serve distinct but complementary functions in secretion...
  17. pmc Concurrent inhibition of kit- and FcepsilonRI-mediated signaling: coordinated suppression of mast cell activation
    Bettina M Jensen
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11C206, 10 Center Drive, MSC 1881, Bethesda, MD 20892 1881, USA
    J Pharmacol Exp Ther 324:128-38. 2008
    ....
  18. pmc Prevention of F-actin assembly switches the response to SCF from chemotaxis to degranulation in human mast cells
    Daniel Smrz
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
    Eur J Immunol 43:1873-82. 2013
    ..These observations suggest that processes regulating cell migration limit MC degranulation as a consequence of cytoskeletal reorganization. ..
  19. pmc A truncated splice-variant of the FcεRIβ receptor subunit is critical for microtubule formation and degranulation in mast cells
    Glenn Cruse
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 38:906-17. 2013
    ..Because t-FcεRIβ has this critical function, it represents a therapeutic target for the downregulation of allergic inflammation...
  20. pmc Prostaglandin E2 activates and utilizes mTORC2 as a central signaling locus for the regulation of mast cell chemotaxis and mediator release
    Hye Sun Kuehn
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 286:391-402. 2011
    ..These findings are consistent with the conclusion that activation of mTORC2, downstream of PI3K, represents a critical signaling locus for chemotaxis and chemokine release from PGE(2)-activated mast cells...
  21. pmc Btk-dependent Rac activation and actin rearrangement following FcepsilonRI aggregation promotes enhanced chemotactic responses of mast cells
    Hye Sun Kuehn
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive MSC 1881, Bethesda, MD 20892 1881, USA
    J Cell Sci 123:2576-85. 2010
    ..Taken together, these data demonstrate that, by regulating signaling pathways that control F-actin rearrangement, Btk is crucial for the ability of antigen to amplify mast-cell chemotactic responses...
  22. pmc Mechanism of upregulation of the inhibitory regulator, src-like adaptor protein (SLAP), by glucocorticoids in mast cells
    Seung Kiel Park
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1760, USA
    Mol Immunol 46:492-7. 2009
    ..In the case of SLAP specifically, this requires activation of gene transcription through the interaction of the glucocorticoid receptor with GRE...
  23. ncbi request reprint Dexamethasone up-regulates the inhibitory adaptor protein Dok-1 and suppresses downstream activation of the mitogen-activated protein kinase pathway in antigen-stimulated RBL-2H3 mast cells
    Takaaki Hiragun
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1760, USA
    Mol Pharmacol 67:598-603. 2005
    ..These findings identify Dok-1 as mediator of the antiallergic actions of dexamethasone and as a negative regulator of the MAP kinase pathway and downstream release of inflammatory mediators...
  24. pmc Knockout of the Trpc1 gene reveals that TRPC1 can promote recovery from anaphylaxis by negatively regulating mast cell TNF-α production
    Nevenka Medic
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive MSC 1881, Bethesda, MD 20892 1881, USA
    Cell Calcium 53:315-26. 2013
    ..These data thus provide evidence that, in this model, TRPC1 promotes recovery from the anaphylactic response by repressing antigen-mediated TNF-α release from MCs...
  25. pmc Distinct PGE2-responder and non-responder phenotypes in human mast cell populations: "all or nothing" enhancement of antigen-dependent mediator release
    Hye Sun Kuehn
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1881, USA
    Immunol Lett 141:45-54. 2011
    ..However, translocation of PLCγ(1) to the cell membrane and the associated calcium signal were enhanced only in the responder HuMC population indicating that the link between EP3 and PLCγ is impaired in the non-responder HuMCs...
  26. ncbi request reprint Dexamethasone suppresses antigen-induced activation of phosphatidylinositol 3-kinase and downstream responses in mast cells
    Marcus V M Andrade
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 172:7254-62. 2004
    ....
  27. ncbi request reprint The phospholipase C gamma 1-dependent pathway of Fc epsilon RI-mediated mast cell activation is regulated independently of phosphatidylinositol 3-kinase
    Christine Tkaczyk
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 278:48474-84. 2003
    ..However, PI 3-kinase may contribute to the later phase of Fc epsilon RI-mediated degranulation in human mast cells...
  28. ncbi request reprint Mastoparan selectively activates phospholipase D2 in cell membranes
    Ahmed Chahdi
    Laboratory of Molecular Immunology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892 1760, USA
    J Biol Chem 278:12039-45. 2003
    ..Therefore, mastoparan may be useful for investigating the regulation of PLD2, particularly in view of the well studied molecular interactions of mastoparan with certain other strategic signaling proteins...
  29. ncbi request reprint Cutting Edge: Lentiviral short hairpin RNA silencing of PTEN in human mast cells reveals constitutive signals that promote cytokine secretion and cell survival
    Yasuko Furumoto
    Molecular Inflammation Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 176:5167-71. 2006
    ..The findings demonstrate that PTEN functions as a key regulator of mast cell homeostasis and FcepsilonRI-responsiveness...
  30. ncbi request reprint Regulation of phospholipase D and secretion in mast cells by protein kinase A and other protein kinases
    Wahn Soo Choi
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 1760, USA
    Ann N Y Acad Sci 968:198-212. 2002
    ..The pathological/physiological implications of the regulation of PLD by PKA require further evaluation in other cell systems...
  31. ncbi request reprint Cutting edge: dexamethasone negatively regulates Syk in mast cells by up-regulating SRC-like adaptor protein
    Takaaki Hiragun
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 177:2047-50. 2006
    ..The induction of these inhibitory regulators may contribute to the immunosuppressive activity of dexamethasone in mast cells...
  32. pmc Amplification of cytokine production through synergistic activation of NFAT and AP-1 following stimulation of mast cells with antigen and IL-33
    Marcus V Andrade
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1760, USA
    Eur J Immunol 41:760-72. 2011
    ..IL-33 may retune mast cell responses to Ag toward enhanced cytokine production and thus determine the symptoms and severity of Ag-dependent allergic and autoimmune diseases...
  33. pmc Regulation of Ca2+ signaling with particular focus on mast cells
    Hong Tao Ma
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
    Crit Rev Immunol 29:155-86. 2009
    ....
  34. pmc Examination of the role of TRPM8 in human mast cell activation and its relevance to the etiology of cold-induced urticaria
    Nevenka Medic
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1881, USA
    Cell Calcium 50:473-80. 2011
    ..From these data, we conclude that TRPM8 is unlikely to directly regulate mast cell activation in cold urticaria. Thus, alternative mechanisms likely exist for the pathogenesis of this disease...
  35. doi request reprint Regulators of Ca(2+) signaling in mast cells: potential targets for treatment of mast cell-related diseases?
    Hong Tao Ma
    Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA
    Adv Exp Med Biol 716:62-90. 2011
    ....
  36. pmc Regulation of mast cell responses in health and disease
    Alasdair M Gilfillan
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1881, USA
    Crit Rev Immunol 31:475-529. 2011
    ....
  37. ncbi request reprint Phospholipases D1 and D2 regulate different phases of exocytosis in mast cells
    Wahn Soo Choi
    Laboratory of Molecular Immunology and Light Microscopy Core Facility, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 168:5682-9. 2002
    ....
  38. ncbi request reprint Characterization of novel stem cell factor responsive human mast cell lines LAD 1 and 2 established from a patient with mast cell sarcoma/leukemia; activation following aggregation of FcepsilonRI or FcgammaRI
    Arnold S Kirshenbaum
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1881, USA
    Leuk Res 27:677-82. 2003
    ..Both LAD 1 and 2 release beta-hexosaminidase following FcepsilonRI or FcgammaRI aggregation. The availability of these cell lines offers an unparalleled circumstance to examine the biology of human mast cells...
  39. pmc Phospholipase D2 acts as an essential adaptor protein in the activation of Syk in antigen-stimulated mast cells
    Jun Ho Lee
    Department of Immunology, College of Medicine, Konkuk University, Chungju 380 701, Korea
    Blood 108:956-64. 2006
    ..Apparently, the interaction of PLD2 with Syk is an early critical event in the activation of mast cells...
  40. pmc Role of ABCC1 in export of sphingosine-1-phosphate from mast cells
    Poulami Mitra
    Department of Biochemistry, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA
    Proc Natl Acad Sci U S A 103:16394-9. 2006
    ..Transport of S1P by ABCC1 influenced migration of mast cells toward antigen but not degranulation. These findings have important implications for S1P functions in mast cell-mediated immune responses...
  41. doi request reprint Curcumin, a constituent of curry, suppresses IgE-mediated allergic response and mast cell activation at the level of Syk
    Jun Ho Lee
    Department of Immunology and Physiology, College of Medicine, Konkuk University, Chungju, Korea
    J Allergy Clin Immunol 121:1225-31. 2008
    ..Curcumin can block this activation, but the mechanism and the effects of curcumin on IgE-mediated allergic reactions are unknown...