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The protein tyrosine kinase Tec regulates mast cell function
Authors:Uwe Schmidt  Anastasia Abramova  Nicole Boucheron  Eva Eckelhart  Alexandra Schebesta  Ivan Bilic  Michael Kneidinger  Bernd Unger  Martina Hammer  Maria Sibilia  Peter Valent  Wilfried Ellmeier
Affiliation:1. Division of Immunobiology, Institute of Immunology, Center for Physiology, Pathophysiology and Immunology, Medical University of Vienna, Austria;2. Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria;3. Competence Center for Biomolecular Therapeutics (BMT), Vienna, Austria;4. Cancer Research Institute, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
Abstract:Mast cells play crucial roles in a variety of normal and pathophysiological processes and their activation has to be tightly controlled. Here, we demonstrate that the protein tyrosine kinase Tec is a crucial regulator of murine mast cell function. Tec was activated upon FcεRI stimulation of BM‐derived mast cells (BMMC). The release of histamine in the absence of Tec was normal in vitro and in vivo; however, leukotriene C4 levels were reduced in Tec?/? BMMC. Furthermore, the production of IL‐4 was severely impaired, and GM‐CSF, TNF‐α and IL‐13 levels were also diminished. Finally, a comparison of WT, Tec?/?, Btk?/? and Tec?/?Btk?/? BMMC revealed a negative role for Btk in the regulation of IL‐4 production, while for the efficient production of TNF‐α, IL‐13 and GM‐CSF, both Tec and Btk were required. Our results demonstrate a crucial role for Tec in mast cells, which is partially different to the function of the well‐characterized family member Btk.
Keywords:Kinases  Knockout mice  Mast cells  Signal transduction
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