Positive Regulation of c-Jun N-Terminal Kinase and TNF-α Production But Not Histamine Release by SHP-1 in RBL-2H3 Mast Cells

Positive Regulation of c-Jun N-Terminal Kinase and TNF-α Production But Not Histamine Release by SHP-1 in RBL-2H3 Mast Cells
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SHP-1 在 RBL-2H3 肥大细胞中正向调节 c-Jun N 末端激酶和 TNF-α 的产生,但不调节组胺的释放

DOI:
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发表时间:
2000
影响因子:
4.4
通讯作者:
R. Siraganian
R. Siraganian
中科院分区:
医学2区
文献类型:
--
作者:
Z. Xie;Juan Zhang;R. Siraganian

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The SH2-containing protein tyrosine phosphatase1 (SHP-1) is important for signaling from immune receptors. To investigate the role of SHP-1 in mast cells we overexpressed the wild-type and the phosphatase-inactive forms of SHP-1 in rat basophilic leukemia 2H3 (RBL-2H3) mast cell line. The phosphatase-inactive SHP-1 (C453S or D419A) retains its ability to bind tyrosine phosphorylated substrates and thereby competes with the endogenous wild-type enzyme. Overexpression of wild-type SHP-1 decreased the FcεRI aggregation-induced tyrosine phosphorylation of the β and γ subunits of the receptor whereas the dominant negative SHP-1 enhanced phosphorylation. There were also similar changes in the tyrosine phosphorylation of Syk. However, receptor-induced histamine release in the cells expressing either wild-type or dominant negative SHP-1 was similar to that in the parental control cells. In contrast, compared with the parental RBL-2H3 cells, FcεRI-induced c-Jun N-terminal kinase phosphorylation and the level of TNF-α mRNA was increased in the cells overexpressing wild-type SHP-1 whereas the dominant negative SHP-1 had the opposite effect. The substrate-trapping mutant SHP1/D419A identified pp25 and pp30 as two major potential substrates of SHP-1 in RBL-2H3 cells. Therefore, SHP-1 may play a role in allergy and inflammation by regulating mast cell cytokine production.
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