The Yersinia Virulence Factor YopM Hijacks Host Kinases to Inhibit Type III Effector-Triggered Activation of the Pyrin Inflammasome.
The Yersinia Virulence Factor YopM Hijacks Host Kinases to Inhibit Type III Effector-Triggered Activation of the Pyrin Inflammasome.
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DOI：
10.1016/j.chom.2016.07.018
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发表时间：
2016-09-14
影响因子：
30.3
通讯作者：
Bliska JB
中科院分区：
文献类型：
--
作者：
Chung LK;Park YH;Zheng Y;Brodsky IE;Hearing P;Kastner DL;Chae JJ;Bliska JB
Pathogenic Yersinia, including Y. pestis, the agent of plague in humans, and Y. pseudotuberculosis, the related enteric pathogen, deliver virulence effectors into host cells via a prototypical type III secretion system to promote pathogenesis. These effectors, termed Yersinia outer proteins (Yops), modulate multiple host signaling responses. Studies in Y. pestis and Y. pseudotuberculosis have shown that YopM suppresses infection-induced inflammasome activation, however the underlying molecular mechanism is largely unknown. Here we show that YopM specifically restricts the pyrin inflammasome, which is triggered by the RhoA-inactivating enzymatic activities of YopE and YopT, in Y. pseudotuberculosis-infected macrophages. The attenuation of a yopM mutant is fully reversed in pyrin knock-out mice, demonstrating that YopM inhibits pyrin to promote virulence. Mechanistically, YopM recruits and activates the host kinases PRK1 and PRK2 to negatively regulate pyrin by phosphorylation. These results show how a virulence factor can hijack host kinases to inhibit effector-triggered pyrin inflammasome activation. Pathogenic Yersinia secrete effectors called Yops, which can trigger or inhibit protective immune responses. Chung et al. demonstrate that both YopE and YopT inactivate RhoA, resulting in activation of the pyrin inflammasome. Consequently, Yersinia maintain virulence by delivering YopM, which hijacks host kinases to phosphorylate pyrin and inhibit inflammasome activation.
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影响因子：
6.7
作者：
Dumas A;Amiable N;de Rivero Vaccari JP;Chae JJ;Keane RW;Lacroix S;Vallières L
通讯作者：
Vallières L
影响因子：
4
作者：
Falk MD;Liu W;Bolaños B;Unsal-Kacmaz K;Klippel A;Grant S;Brooun A;Timofeevski S
通讯作者：
Timofeevski S
影响因子：
4.8
作者：
McDonald, C;Vacratsis, PO;Dixon, JE
通讯作者：
Dixon, JE
DOI：
10.4049/jimmunol.1102272
发表时间：
2012-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Gavrilin MA;Abdelaziz DH;Mostafa M;Abdulrahman BA;Grandhi J;Akhter A;Abu Khweek A;Aubert DF;Valvano MA;Wewers MD;Amer AO
通讯作者：
Amer AO
影响因子：
30.5
作者：
Akula MK;Shi M;Jiang Z;Foster CE;Miao D;Li AS;Zhang X;Gavin RM;Forde SD;Germain G;Carpenter S;Rosadini CV;Gritsman K;Chae JJ;Hampton R;Silverman N;Gravallese EM;Kagan JC;Fitzgerald KA;Kastner DL;Golenbock DT;Bergo MO;Wang D
通讯作者：
Wang D