Research Topics
Genomes and Genes
| Toshiaki KawakamiSummaryAffiliation: La Jolla Institute for Allergy and Immunology Country: USA Publications
Research Grants
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Detail Information
Publications
Mast cell survival and activation by IgE in the absence of antigen: a consideration of the biologic mechanisms and relevanceToshiaki Kawakami
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA
J Immunol 175:4167-73. 2005....
[Regulation of mast cell survival and activation by monomeric IgE]Toshiaki Kawakami
La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA
Arerugi 53:557-61. 2004- Protein kinase C beta (PKC beta): normal functions and diseasesToshiaki Kawakami
Division of Allergy, La Jolla Institute for Allergy and Immunology, Science Center Drive, San Diego, California 92121, USA
J Biochem 132:677-82. 2002..Their involvement in disorders due to pertubations in these signaling systems, i.e., immunodeficiencies and diabetes, is also reviewed. Finally, patterns of PKC action in these and other biologic systems are discussed... - Mast cells in atopic dermatitisToshiaki Kawakami
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA
Curr Opin Immunol 21:666-78. 2009..Numerous animal models have been used to study this epidemic disease. Here we review the recent progress to synthesize our current understanding of this disease and potential mechanisms for a mast cell's role in the disease... - The Src family kinase Hck regulates mast cell activation by suppressing an inhibitory Src family kinase LynHong 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... - Positive and negative regulation of mast cell activation by Lyn via the FcepsilonRIWenbin 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... - Regulation of highly cytokinergic IgE-induced mast cell adhesion by Src, Syk, Tec, and protein kinase C family kinasesJiro 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... - Protein kinase C betaII regulates Akt phosphorylation on Ser-473 in a cell type- and stimulus-specific fashionYuko Kawakami
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA
J Biol Chem 279:47720-5. 2004..Therefore, PKCbetaII appears to work as a cell type- and stimulus-specific PDK2... - Lyn- and PLC-beta3-dependent regulation of SHP-1 phosphorylation controls Stat5 activity and myelomonocytic leukemia-like diseaseWenbin Xiao
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA
Blood 116:6003-13. 2010..Therefore, we identify a novel Lyn/PLC-β3-mediated regulatory mechanism of SHP-1 and Stat5 activities... - Phospholipase C-β3 regulates FcɛRI-mediated mast cell activation by recruiting the protein phosphatase SHP-1Wenbin Xiao
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA
Immunity 34:893-904. 2011..Thus, we have defined a PLC-β3- and SHP-1-mediated signaling pathway for FcɛRI-mediated cytokine production... - Early divergence of Fc epsilon receptor I signals for receptor up-regulation and internalization from degranulation, cytokine production, and survivalJiro 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... - Regulation of myeloproliferation and M2 macrophage programming in mice by Lyn/Hck, SHIP, and Stat5Wenbin 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... - A minor catalytic activity of Src family kinases is sufficient for maximal activation of mast cells via the high-affinity IgE receptorMichael Poderycki
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA
J Immunol 184:84-93. 2010..Furthermore, the data suggest that both positive and negative regulatory functions of Lyn are predominantly carried out by its catalytic activity and not an adaptor function... - Pivotal advance: IgE accelerates in vitro development of mast cells and modifies their phenotypeJun ichi Kashiwakura
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA
J Leukoc Biol 84:357-67. 2008..Therefore, our results suggest that monomeric IgEs, especially HC IgEs, not only promote mast cell development but also modulate the mast cell phenotype... - Dysregulation of Src family kinases in mast cells from epilepsy-resistant ASK versus epilepsy-prone EL miceJiro Kitaura
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA
J Immunol 178:455-62. 2007.... - Short Stat5-interacting peptide derived from phospholipase C-β3 inhibits hematopoietic cell proliferation and myeloid differentiationHiroki Yasudo
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America
PLoS ONE 6:e24995. 2011.... - IgE- and IgE+Ag-mediated mast cell migration in an autocrine/paracrine fashionJiro 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... - Tumor suppression by phospholipase C-beta3 via SHP-1-mediated dephosphorylation of Stat5Wenbin Xiao
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA
Cancer Cell 16:161-71. 2009..The same mechanism for malignant transformation seems to be operative in other human lymphoid and myeloid malignancies. Thus, PLC-beta3 is likely a tumor suppressor... - Evidence that IgE molecules mediate a spectrum of effects on mast cell survival and activation via aggregation of the FcepsilonRIJiro 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... - Polyclonal IgE induces mast cell survival and cytokine productionJun ichi Kashiwakura
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, CA, USA
Allergol Int 58:411-9. 2009..However, no studies have been performed on the effects of polyclonal IgE molecules. Here, we tested whether polyclonal mouse and human IgE molecules affect survival and cytokine production in mast cells... - Regulation of dendritic cell maturation and function by Bruton's tyrosine kinase via IL-10 and Stat3Yuko Kawakami
Divisions of Cell Biology and Molecular Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA
Proc Natl Acad Sci U S A 103:153-8. 2006..These negative regulatory functions of Btk in dendritic cells appear to be mediated mainly through autocrine secretion of IL-10 and subsequent activation of Stat3... - Histamine-releasing factor has a proinflammatory role in mouse models of asthma and allergyJun chi Kashiwakura
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA
J Clin Invest 122:218-28. 2012..These results indicate that HRF has a proinflammatory role in asthma and skin immediate hypersensitivity, leading us to suggest HRF as a potential therapeutic target... - IgE regulation of mast cell survival and functionToshiaki Kawakami
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, California 92121, USA
Novartis Found Symp 271:100-7; discussion 108-14, 145-51. 2005..Consistent with receptor aggregation induced by monomeric IgE, other means of receptor aggregation, e.g. IgE+antigen and IgE+anti-IgE, can also induce survival and other events in unique ranges of stimulation intensity... - Costimulation of mast cells by 4-1BB, a member of the tumor necrosis factor receptor superfamily, with the high-affinity IgE receptorHajime Nishimoto
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Dr, San Diego, CA 92121, USA
Blood 106:4241-8. 2005..Therefore, FcepsilonRI-inducible 4-1BB plays a costimulatory function together with FcepsilonRI stimulation... - Inhibition of NK cell activity by IL-17 allows vaccinia virus to induce severe skin lesions in a mouse model of eczema vaccinatumYuko Kawakami
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA
J Exp Med 206:1219-25. 2009..Given low NK cell activities and increased IL-17 expression in atopic dermatitis patients, these results can explain the increased susceptibility of atopic dermatitis patients to eczema vaccinatum... - Protective murine and human monoclonal antibodies against eczema vaccinatumYoshiaki Tomimori
Division of Cell Biology, La Jolla Institute for Allergy and Immunology LIAI, La Jolla, CA, USA
Antivir Ther 16:67-75. 2011..Eczema vaccinatum is the most common severe pathology associated with smallpox vaccination (vaccinia virus), occurring at high rates among individuals with a previous history of atopic dermatitis (atopic eczema)... - Techniques to study Fc epsilonRI signalingYuko Kawakami
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA, USA
Methods Mol Biol 315:175-89. 2006..As signal transduction is highly dependent on protein-protein interactions, we will describe experimental details of co-immunoprecipitation methods that are used to confirm such interactions... - JNK1 controls mast cell degranulation and IL-1{beta} production in inflammatory arthritisMonica Guma
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Pathology, Division of Rheumatology, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA
Proc Natl Acad Sci U S A 107:22122-7. 2010..Hence, JNK1 controls mast cell degranulation and FcγR-triggered IL-1β production, in addition to regulating cytokine and matrix metalloproteinase biosynthesis, and is an attractive therapeutic target in inflammatory arthritis... - Critical role for galectin-3 in airway inflammation and bronchial hyperresponsiveness in a murine model of asthmaRiaz I Zuberi
Division of Allergy, La Jolla Institute of Allergy and Immunology, San Diego, California, USA
Am J Pathol 165:2045-53. 2004..We conclude that galectin-3 may play an important role in the pathogenesis of asthma and inhibitors of this lectin may prove useful for treatment of this disease... 
Monomeric IgE and mast cell development, survival and functionJun ichi Kashiwakura
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA
Adv Exp Med Biol 716:29-46. 2011....- An improved mouse model of atopic dermatitis and suppression of skin lesions by an inhibitor of Tec family kinasesYuko Kawakami
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA
Allergol Int 56:403-9. 2007..We attempted to develop an improved method to induce an animal model of atopic dermatitis and to use it to evaluate the efficacy of a Tec family kinase inhibitor... - Most Highly Cytokinergic IgEs Have Polyreactivity to AutoantigensJun ichi Kashiwakura
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Science, Itabashi ku, Tokyo, Japan
Allergy Asthma Immunol Res 4:332-40. 2012..In this study, we investigated whether IgEs recognize autoantigens and whether IgEs' binding of autoantigens correlates with difference s in HC versus PC properties... - Regulation of mast-cell and basophil function and survival by IgEToshiaki Kawakami
Division of Allergy, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, California 92121, USA
Nat Rev Immunol 2:773-86. 2002..So, the binding of IgE to Fc epsilon RI might influence mast-cell and basophil survival directly or indirectly, and can also regulate cellular function... - A novel role for the transcription factor HIF-1α in the formation of mast cell extracellular trapsKatja Branitzki-Heinemann
Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA
Biochem J 446:159-63. 2012.... - A Ras activation pathway dependent on Syk phosphorylation of protein kinase CYuko Kawakami
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 100:9470-5. 2003..By recruiting the Grb-2/Sos complex to the plasma membrane, these conventional PKC isoforms contribute to the full activation of the Ras/extracellular signal-regulated kinase signaling pathway in FcepsilonRI-stimulated mast cells... - Regulation of outside-in signaling in platelets by integrin-associated protein kinase C betaCharito S Buensuceso
Hematology-Oncology Division, Department of Medicine, University of California San Diego, La Jolla, California 92093, USA
J Biol Chem 280:644-53. 2005..Furthermore, the studies extend the concept of alpha(IIb)beta(3) as a scaffold for multiple protein kinases that regulate the platelet actin cytoskeleton... - Identification and characterization of a new pair of immunoglobulin-like receptors LMIR1 and 2 derived from murine bone marrow-derived mast cellsHidetoshi Kumagai
Division of Hematopoietic Factors, The Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, 6 1 Shirokanedai 4 chome, Minato ku, Tokyo 108 8639, Japan
Biochem Biophys Res Commun 307:719-29. 2003..These findings suggest that a new pair of ITIM/ITAM-bearing receptors, LMIR1 and 2, regulate mast cell-mediated inflammatory responses through yet to be defined ligand(s)... - Human IgE+ and IgE- are not equivalent to mouse highly cytokinergic IgELiping Xie
Johns Hopkins Asthma and Allergy Center at Johns Hopkins University School of Medicine, Baltimore, MD, USA
J Allergy Clin Immunol 121:1027-33. 2008..Recently, there have been reports of monomeric highly cytokinergic IgEs causing mediator release, cytokine release, and phosphorylation events in cultured rodent and human mast cells in the absence of antigen... - G-protein-coupled receptor signaling in Syk-deficient neutrophils and mast cellsAttila 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... - O-methylated catechins from tea leaves inhibit multiple protein kinases in mast cellsMari Maeda-Yamamoto
National Institute of Vegetable and Tea Science, National Agriculture Research Organization, and School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
J Immunol 172:4486-92. 2004..These observations for the first time have revealed the molecular mechanisms of antiallergic effects of tea-derived catechins... - Partial depletion of intracellular ATP mediates the stress-survival function of the PCPH oncoproteinJuan A Recio
Laboratory of Experimental Carcinogenesis, Department of Radiation Medicine, Georgetown University Medical Center, Washington, DC 20007, USA
Cancer Res 62:2690-4. 2002..Treatment with adenosine or nucleoside analogues may thus enhance the response to radiation or chemotherapy of tumors that express the PCPH oncogene... - Role of the FcepsilonRI beta-chain ITAM as a signal regulator for mast cell activation with monomeric IgESatoshi Nunomura
Division of Molecular Cell Immunology and Allergology, Nihon University School of Medicine, Itabashi ku, Tokyo 173 8910, Japan
Int Immunol 17:685-94. 2005..These findings for the first time revealed the unique functions of the beta-chain ITAM in both chemical mediator release and cytokine production of mast cells upon monomeric IgE stimulation... - Monomeric IgE enhances human mast cell chemokine production: IL-4 augments and dexamethasone suppresses the responseKentaro Matsuda
Department of Pathology, Stanford University School of Medicine, CA 94305-5324, USA
J Allergy Clin Immunol 116:1357-63. 2005.... - Fer and Fps/Fes participate in a Lyn-dependent pathway from FcepsilonRI to platelet-endothelial cell adhesion molecule 1 to limit mast cell activationChristian M Udell
Department of Biochemistry, Queen s University, Kingston, Ontario, Canada
J Biol Chem 281:20949-57. 2006..Thus, Lyn and Fer/Fps kinases cooperate to phosphorylate Pecam-1 and activate Shp1/Shp2 phosphatases that function in part to limit mast cell activation... - Development, migration, and survival of mast cellsYoshimichi Okayama
Research Unit for Allergy Transcriptome, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama, Japan
Immunol Res 34:97-115. 2006..Recent studies also demonstrated that monomeric IgE binding to FcepsilonRI can enhance mast-cell survival. In this review we discuss the factors that regulate mast cell development, migration, and survival... - PKC-beta controls I kappa B kinase lipid raft recruitment and activation in response to BCR signalingThomas T Su
The Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA
Nat Immunol 3:780-6. 2002..Together, these data define an essential role for PKC-beta in BCR survival signaling and highlight PKC-beta as a key therapeutic target for B-lineage malignancies... - Role of galectin-3 in mast cell functions: galectin-3-deficient mast cells exhibit impaired mediator release and defective JNK expressionHuan Yuan Chen
Department of Dermatology, School of Medicine, University of California Davis, Sacramento, CA 95817, USA
J Immunol 177:4991-7. 2006..All together, these results point to an important role of galectin-3 in mast cell biology... - Quantitative time-resolved phosphoproteomic analysis of mast cell signalingLulu Cao
Department of Chemistry, Brown University, Providence, RI 02912, USA
J Immunol 179:5864-76. 2007....
Research Grants
- Regulation of asthma by Btk and family kinasesToshiaki Kawakami; Fiscal Year: 2007..This is a poorly explored area in DC biology. Our efforts will hopefully identify novel targets for pharmaceutical intervention to treat asthma and other immune diseases. ..
- Mast cell regulation by PKC and AktToshiaki Kawakami; Fiscal Year: 2005..Given the critical importance of PKC in degranulation and other activation events, these studies are also likely to provide an opportunity for novel therapeutic modalities aimed at allergic diseases. ..
- IgE Regulation of Mast Cell Growth and SurvivalToshiaki Kawakami; Fiscal Year: 2006..abstract_text> ..
- ROLES OF PH DOMAINS IN MAST CELL SIGNAL TRANSDUCTIONToshiaki Kawakami; Fiscal Year: 2000....
- PROTEIN TYROSINE KINASES AND MAST CELL ACTIVATIONToshiaki Kawakami; Fiscal Year: 2001..Particularly, interactions of Btk with Src PTKs and ERK might suggest positive and negative, respectively, feedback mechanisms for FceRI induced mast cell activation. ..