International Immunology, Vol. 12, No. 2, 169-176,
February 2000
© 2000 Japanese Society for Immunology
Regulation of mast cell signaling through high-affinity IgE receptor by CD45 protein tyrosine phosphatase
Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan
Correspondence to: T. Yamashita
The transmembrane tyrosine phosphatase CD45 regulates the activity of src family protein tyrosine kinases (PTK) and thereby influences the signaling via such receptors as T and B cell antigen receptors associated with these PTK. However, its implication in signaling through the mast cell receptor with high affinity for IgE (Fc
RI) is less clear, although Lyn, a member of the src family, plays an important role in FcRI-mediated signaling. To define a role for CD45 in FcRI signal transduction, we established CD45 high expressing rat basophilic leukemia cell lines (RBL-CD45H) and cell lines expressing trace amounts of CD45 (RBL-CD45L). We demonstrate that although all RBL-CD45L cell lines degranulate following IgE- and antigen-induced FcRI aggregation, the response is significantly reduced at a low dose of antigen. The cells show a delayed and slowed Ca2+ mobilization even though at a higher dose where the cells degranulate to a similar extent as RBL-CD45H. This diminished Ca2+ response is restored by reconstitution of RBL-CD45L with a chimeric molecule containing the cytoplasmic phosphatase domains of rat CD45. Furthermore, tyrosine phosphorylation of FcRI, association of FcRI with Lyn and PTK activity associated with FcRI, all of which are enhanced upon FcRI aggregation in RBL-CD45H, are impaired in RBL-CD45L. Finally, we show that FcRI is physically associated with CD45 in RBL-CD45H prior to receptor aggregation. Thus, we propose that, although not indispensable in mast cell degranulation, CD45 positively regulates the signaling through FcRI by promoting the activation of FcRI-associated Lyn.
Keywords: Fc
RI, Lyn, tyrosine phosphorylation, rat basophilic leukemia
Transmitting editor: D. Kitamura
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