TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway
TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway
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DOI：
10.1101/gad.17224711
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发表时间：
2011-10-01
影响因子：
10.5
通讯作者：
Davis, Roger J.
中科院分区：
文献类型：
--
作者：
Kant, Shashi;Swat, Wojciech;Davis, Roger J.
对肿瘤坏死因子（TNF）的生物学应答涉及MAP激酶的激活。在这里，我们报告的机制，MAP激酶激活的TNF是由Rho GTdR家族成员Rac/Cdc 42介导的。该信号通路需要鸟苷核苷酸交换因子Vav的Src依赖性活化、Rac/Cdc 42的活化以及混合谱系蛋白激酶（MLK）上的Rac/Cdc 42相互作用位点（CRIB基序）的接合。我们表明，这一途径是必不可少的充分MAP激酶激活过程中的响应TNF。此外，这种MLK途径有助于体内炎症。
The biological response to tumor necrosis factor (TNF) involves activation of MAP kinases. Here we report a mechanism of MAP kinase activation by TNF that is mediated by the Rho GTPase family members Rac/Cdc42. This signaling pathway requires Src-dependent activation of the guanosine nucleotide exchange factor Vav, activation of Rac/Cdc42, and the engagement of the Rac/Cdc42 interaction site (CRIB motif) on mixed-lineage protein kinases (MLKs). We show that this pathway is essential for full MAP kinase activation during the response to TNF. Moreover, this MLK pathway contributes to inflammation in vivo.