MISC

2009年5月

Protein Tyrosine Phosphatase epsilon is a Negative Regulator of Fc epsilon RI-mediated Mast Cell Responses

SCANDINAVIAN JOURNAL OF IMMUNOLOGY
  • M. Akimoto
  • ,
  • K. Mishra
  • ,
  • K. -T. Lim
  • ,
  • N. Tani
  • ,
  • S. -i. Hisanaga
  • ,
  • T. Katagiri
  • ,
  • A. Elson
  • ,
  • K. Mizuno
  • ,
  • H. Yakura

69
5
開始ページ
401
終了ページ
411
記述言語
英語
掲載種別
DOI
10.1111/j.1365-3083.2009.02235.x
出版者・発行元
WILEY-BLACKWELL PUBLISHING, INC

Modulation of mast-cell activation may provide novel ways to control allergic diseases. Here, we show that protein tyrosine phosphatase epsilon (PTP epsilon; Ptpre) plays key regulatory roles during mast-cell activation mediated by the high-affinity IgE receptor (Fc epsilon RI). Bone marrow-derived mast cells (BMMC) from Ptpre(-/-) mice exhibited enhanced Fc epsilon RI-induced Ca(2+) mobilization and mitogen-activated protein kinase (MAPK) (JNK and p38) activation, and showed corresponding enhancement of evoked degranulation and cytokine production, but not leukotriene production. Examination of proteins linking tyrosine kinase activation and Ca(2+) mobilization revealed that the absence of PTP epsilon leads to increased phosphorylation of the linker for activation of T cells and SH2 domain-containing leucocyte phosphoproteins of 76 kDa, but not Grb2-associated binder-2 (Gab2). Because Gab2 is considered to be situated downstream of Fyn kinase, we reasoned that Fyn may not be a target of PTP epsilon. In the event, Syk but not Lyn was hyperphosphorylated in PTP epsilon-deficient BMMC. Thus, PTP epsilon most likely exerts its effects at the level of Syk, inhibiting downstream events including phosphorylation of SLP-76 and linker of activated T cells and mobilization of Ca(2+). Consistent with the in vitro data, antigen- and IgE-mediated passive systemic anaphylactic reactions were augmented in Ptpre(-/-) mice. Given that the number of mast cells is unchanged in these mice, this observation most likely reflects alterations of mast cell-autonomous signalling events. These data suggest that PTP epsilon negatively regulates Fc epsilon RI-mediated signalling pathways and thus constitutes a novel target for ameliorating allergic conditions.

Web of Science ® 被引用回数 : 14

リンク情報
DOI
https://doi.org/10.1111/j.1365-3083.2009.02235.x
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000265039300002&DestApp=WOS_CPL

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