We investigated the role of Bruton's tyrosine kinase (Btk) in FcεRI-dependent activation of mouse mast cells, using xid and btk null mutant mice. Unlike B cell development, mast cell development is apparently normal in these btk mutant mice. However, mast cells derived from these mice exhibited significant abnormalities in FcεRI-dependent function. xid mice primed with anti-dinitrophenyl monoclonal IgE antibody exhibited mildly diminished early-phase and severely blunted late-phase anaphylactic reactions in response to antigen challenge in vivo. Consistent with this finding, cultured mast cells derived from the bone marrow cells of xid or btk null mice exhibited mild impairments in degranulation, and more profound defects in the production of several cytokines, upon FcεRI cross-linking. Moreover, the transcriptional activities of these cytokine genes were severely reduced in FcεRI-stimulated btk mutant mast cells. The specificity of these effects of btk mutations was confirmed by the improvement in the ability of btk mutant mast cells to degranulate and to secrete cytokines after the retroviral transfer of wild-type btk cDNA, but not of vector or kinase-dead btk cDNA. Retroviral transfer of Emt (= Itk/Tsk), Btk's closest relative, also partially improved the ability of btk mutant mast cells to secrete mediators. Taken together, these results demonstrate an important role for Btk in the full expression of FcεRI signal transduction in mast cells.
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20 April 1998
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April 20 1998
Involvement of Bruton's Tyrosine Kinase in FcεRI-dependent Mast Cell Degranulation and Cytokine Production
Daisuke Hata,
Daisuke Hata
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
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Yuko Kawakami,
Yuko Kawakami
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
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Naoki Inagaki,
Naoki Inagaki
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
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Chris S. Lantz,
Chris S. Lantz
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
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Toshio Kitamura,
Toshio Kitamura
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
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Wasif N. Khan,
Wasif N. Khan
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
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Mari Maeda-Yamamoto,
Mari Maeda-Yamamoto
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
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Toru Miura,
Toru Miura
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
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Wei Han,
Wei Han
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
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Stephen E. Hartman,
Stephen E. Hartman
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
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Libo Yao,
Libo Yao
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
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Hiroichi Nagai,
Hiroichi Nagai
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
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Anne E. Goldfeld,
Anne E. Goldfeld
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
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Frederick W. Alt,
Frederick W. Alt
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
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Stephen J. Galli,
Stephen J. Galli
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
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Owen N. Witte,
Owen N. Witte
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
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Toshiaki Kawakami
Toshiaki Kawakami
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
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Daisuke Hata
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
Yuko Kawakami
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
Naoki Inagaki
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
Chris S. Lantz
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
Toshio Kitamura
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
Wasif N. Khan
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
Mari Maeda-Yamamoto
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
Toru Miura
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
Wei Han
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
Stephen E. Hartman
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
Libo Yao
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
Hiroichi Nagai
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
Anne E. Goldfeld
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
Frederick W. Alt
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
Stephen J. Galli
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
Owen N. Witte
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
Toshiaki Kawakami
From the *Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121; the ‡Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan; the §Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Hematopoietic Factors, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; the ¶Howard Hughes Medical Institute, Children's Hospital, Enders 861, Boston, Massachusetts 02115; the **Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ††Howard Hughes Medical Institute, University of California, Los Angeles, California 90024-1662
Address correspondence to Toshiaki Kawakami, La Jolla Institute for Allergy and Immunology, 10355 Science Center Dr., San Diego, CA 92121. Phone: 619-558-3500; Fax: 619-558-3526; E-mail: toshi_ [email protected]
1Abbreviations used in this paper: BMMC, bone marrow–derived cultured mast cells; Btk, Bruton's tyrosine kinase; ITAM, immunoreceptor tyrosine–based activation motif; NFAT, nuclear factor of activated T cells; PCA, passive cutaneous anaphylactic; PH, pleckstrin homology; PKC, protein kinase C; PLC, phospholipase C; PTK, protein tyrosine kinase; SCF, stem cell factor; SH, Src homology.
This study was partly supported by National Institutes of Health grants RO1 AI-33617 and RO1 AI-38348 (T. Kawakami) and R37 AI-23990 and RO1 CA-72074 (S.J. Galli) and is Publication No. 147 from the La Jolla Institute for Allergy and Immunology.
Received:
October 01 1997
Revision Received:
January 02 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 187 (8): 1235–1247.
Article history
Received:
October 01 1997
Revision Received:
January 02 1998
Citation
Daisuke Hata, Yuko Kawakami, Naoki Inagaki, Chris S. Lantz, Toshio Kitamura, Wasif N. Khan, Mari Maeda-Yamamoto, Toru Miura, Wei Han, Stephen E. Hartman, Libo Yao, Hiroichi Nagai, Anne E. Goldfeld, Frederick W. Alt, Stephen J. Galli, Owen N. Witte, Toshiaki Kawakami; Involvement of Bruton's Tyrosine Kinase in FcεRI-dependent Mast Cell Degranulation and Cytokine Production . J Exp Med 20 April 1998; 187 (8): 1235–1247. doi: https://doi.org/10.1084/jem.187.8.1235
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