A Chemical Proteomics Approach to Discover Regulators of Innate Immune Signaling.
A Chemical Proteomics Approach to Discover Regulators of Innate Immune Signaling.
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DOI：
10.3390/v15051112
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发表时间：
2023-05-03
期刊：
影响因子：
--
通讯作者：
Johnson JR
中科院分区：
文献类型：
--
作者：
Kurland AP;Bonaventure B;Johnson JR
先天免疫途径受到严格调节，以平衡对感染因子的适当反应和可耐受的炎症水平。先天免疫途径的失调可导致严重的自身炎症性疾病或感染易感性。在这里，我们的目的是确定激酶在共同的细胞途径，调节先天免疫途径相结合的小规模激酶抑制剂筛选定量蛋白质组学。我们发现，激酶ATM，ATR，AMPK和PLK1的抑制剂减少干扰素刺激的基因表达的诱导响应于先天免疫途径激活poly（I：C）转染。然而，这些激酶的siRNA消耗没有验证激酶抑制剂的发现，这表明脱靶效应可以解释它们的活性。我们将激酶抑制剂的作用映射到先天免疫途径的各个阶段。确定激酶抑制剂拮抗这些途径的机制可能会阐明先天免疫途径控制的新机制。
Innate immune pathways are tightly regulated to balance an appropriate response to infectious agents and tolerable levels of inflammation. Dysregulation of innate immune pathways can lead to severe autoinflammatory disorders or susceptibility to infections. Here, we aimed to identify kinases in common cellular pathways that regulate innate immune pathways by combining small-scale kinase inhibitor screening with quantitative proteomics. We found that inhibitors of kinases ATM, ATR, AMPK, and PLK1 reduced the induction of interferon-stimulated gene expression in response to innate immune pathway activation by poly(I:C) transfection. However, siRNA depletion of these kinases did not validate findings with kinase inhibitors, suggesting that off-target effects may explain their activities. We mapped the effects of kinase inhibitors to various stages in innate immune pathways. Determining the mechanisms by which kinase inhibitors antagonize these pathways may illuminate novel mechanisms of innate immune pathway control.
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影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
影响因子：
64.5
作者：
Chevrier N;Mertins P;Artyomov MN;Shalek AK;Iannacone M;Ciaccio MF;Gat-Viks I;Tonti E;DeGrace MM;Clauser KR;Garber M;Eisenhaure TM;Yosef N;Robinson J;Sutton A;Andersen MS;Root DE;von Andrian U;Jones RB;Park H;Carr SA;Regev A;Amit I;Hacohen N
通讯作者：
Hacohen N
影响因子：
14.9
作者：
Perez-Riverol Y;Bai J;Bandla C;García-Seisdedos D;Hewapathirana S;Kamatchinathan S;Kundu DJ;Prakash A;Frericks-Zipper A;Eisenacher M;Walzer M;Wang S;Brazma A;Vizcaíno JA
通讯作者：
Vizcaíno JA
影响因子：
5.8
作者：
Cheng, Alice;Grant, Charles E.;Bailey, Timothy L.
通讯作者：
Bailey, Timothy L.
影响因子：
64.5
作者：
Bouhaddou, Mehdi;Memon, Danish;Krogan, Nevan J.
通讯作者：
Krogan, Nevan J.