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
复制标题
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
作者:
Z. Xie;Juan Zhang;R. Siraganian
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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DOI:
10.1073/pnas.89.3.1123
发表时间:
1992-02-01
影响因子:
11.1
作者:
PLUTZKY, J;NEEL, BG;ROSENBERG, RD
通讯作者:
ROSENBERG, RD
影响因子:
4.4
作者:
S. Johnson;C. Pleiman;Lucy Y. Pao;J. Schneringer;K. Hippen;J. C. Cambier
通讯作者:
S. Johnson;C. Pleiman;Lucy Y. Pao;J. Schneringer;K. Hippen;J. C. Cambier
影响因子:
56.9
作者:
DOODY, GM;JUSTEMENT, LB;FEARON, DT
通讯作者:
FEARON, DT
DOI:
10.1016/s1054-3589(08)60578-5
发表时间:
1996
期刊:
Advances in pharmacology (San Diego, Calif.)
影响因子:
--
作者:
Tonks,NK
通讯作者:
Tonks,NK
DOI:
--
发表时间:
1999
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
作者:
Dustin,LB;Plas,DR;Wong,J;Hu,YT;Soto,C;Chan,AC;Thomas,ML
通讯作者:
Thomas,ML