MKK7 is an essential component of the JNK signal transduction pathway activated by proinflammatory cytokines

被引：296

作者：

Tournier, C

Dong, C

Turner, TK

Jones, SN

Flavell, RA

Davis, RJ ^{[1
]}

机构：

[1] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA

[2] Univ Massachusetts, Sch Med, Dept Biochem & Mol Biol, Program Mol Med, Worcester, MA 01605 USA

[3] Yale Univ, Sch Med, Howard Hughes Med Inst, Immunobiol Sect, New Haven, CT 06520 USA

[4] Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01605 USA

来源：

GENES & DEVELOPMENT | 2001年 / 15卷 / 11期

关键词：

map kinase; tumor necrosis factor; interleukin-1; JNK; MKK4; MKK7;

D O I：

10.1101/gad.888501

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Mitogen-activated protein kinases (MAPK) are activated by phosphorylation on Thr and Tyr by MAPK kinases. Two MAPK kinases (MKK4 and MKK7) can activate the c-run NH2-terminal kinase (JNK) group of MAPK in vitro. TNK is phosphorylated preferentially on Tyr by MKK4 and on Thr by MKK7. Targeted gene-disruption studies in mice were performed to examine the role of MKK4 and MKK7 in vivo. Simultaneous disruption of the Mkk4 and Mkk7 genes was required to block TNK activation caused by exposure of cells to environmental stress. In contrast, disruption of the Mkk7 gene alone was sufficient to prevent TNK activation caused by proinflammatory cytokines. These data demonstrate that MKK4 and MKK7 serve different functions in the JNK signal transduction pathway.

引用

页码：1419 / 1426

页数：8

共 46 条

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