{"title":"细胞内核酸模式识别受体的信号传递对表皮生长因子受体酪氨酸激酶活性的意外需求","authors":"Ganes C Sen, Patricia M Kessler","doi":"10.1089/jir.2023.0016","DOIUrl":null,"url":null,"abstract":"<p><p>Many pattern recognition receptors in mammalian cells initiate signaling processes that culminate in mounting an innate protective response mediated by induced synthesis of a large number of proteins including type I interferons and other cytokines. Many of these receptors are not located on the plasma membrane but on the membranes of intracellular organelles such as endosomes, mitochondria, and the endoplasmic reticulum; they primarily recognize microbial or cellular nucleic acids. In the course of biochemical analyses of the signaling pathways triggered by these receptors, we discovered that they require tyrosine phosphorylation by the protein kinase activity of the epidermal growth factor receptor (EGFR), which is located not only on the plasma membrane but also on the intracellular membranes. Here, we discuss how specific members of this family of receptors, such as TLR3, TLR9, or STING, interact with EGFR and other protein tyrosine kinases and what are the functional consequences of their post-translational modifications. The article highlights an unexpected functional link between a growth factor receptor and cellular innate immune response.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10210212/pdf/","citationCount":"0","resultStr":"{\"title\":\"Unexpected Need of the Epidermal Growth Factor Receptor Tyrosine Kinase Activity for Signaling by Intracellular Pattern Recognition Receptors of Nucleic Acids.\",\"authors\":\"Ganes C Sen, Patricia M Kessler\",\"doi\":\"10.1089/jir.2023.0016\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Many pattern recognition receptors in mammalian cells initiate signaling processes that culminate in mounting an innate protective response mediated by induced synthesis of a large number of proteins including type I interferons and other cytokines. Many of these receptors are not located on the plasma membrane but on the membranes of intracellular organelles such as endosomes, mitochondria, and the endoplasmic reticulum; they primarily recognize microbial or cellular nucleic acids. In the course of biochemical analyses of the signaling pathways triggered by these receptors, we discovered that they require tyrosine phosphorylation by the protein kinase activity of the epidermal growth factor receptor (EGFR), which is located not only on the plasma membrane but also on the intracellular membranes. Here, we discuss how specific members of this family of receptors, such as TLR3, TLR9, or STING, interact with EGFR and other protein tyrosine kinases and what are the functional consequences of their post-translational modifications. The article highlights an unexpected functional link between a growth factor receptor and cellular innate immune response.</p>\",\"PeriodicalId\":16261,\"journal\":{\"name\":\"Journal of Interferon and Cytokine Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2023-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10210212/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Interferon and Cytokine Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1089/jir.2023.0016\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/4/21 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Interferon and Cytokine Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1089/jir.2023.0016","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/4/21 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
哺乳动物细胞中的许多模式识别受体启动了信号传导过程,最终通过诱导合成大量蛋白质(包括 I 型干扰素和其他细胞因子)来启动先天性保护反应。其中许多受体并不位于质膜上,而是位于细胞内细胞器(如内体、线粒体和内质网)的膜上;它们主要识别微生物或细胞核酸。在对这些受体触发的信号通路进行生化分析的过程中,我们发现它们需要表皮生长因子受体(EGFR)的蛋白激酶活性进行酪氨酸磷酸化,而表皮生长因子受体不仅位于质膜上,也位于细胞内膜上。在此,我们将讨论该受体家族的特定成员,如 TLR3、TLR9 或 STING,如何与表皮生长因子受体和其他蛋白酪氨酸激酶相互作用,以及它们的翻译后修饰会产生哪些功能性后果。文章强调了生长因子受体与细胞先天性免疫反应之间意想不到的功能联系。
Unexpected Need of the Epidermal Growth Factor Receptor Tyrosine Kinase Activity for Signaling by Intracellular Pattern Recognition Receptors of Nucleic Acids.
Many pattern recognition receptors in mammalian cells initiate signaling processes that culminate in mounting an innate protective response mediated by induced synthesis of a large number of proteins including type I interferons and other cytokines. Many of these receptors are not located on the plasma membrane but on the membranes of intracellular organelles such as endosomes, mitochondria, and the endoplasmic reticulum; they primarily recognize microbial or cellular nucleic acids. In the course of biochemical analyses of the signaling pathways triggered by these receptors, we discovered that they require tyrosine phosphorylation by the protein kinase activity of the epidermal growth factor receptor (EGFR), which is located not only on the plasma membrane but also on the intracellular membranes. Here, we discuss how specific members of this family of receptors, such as TLR3, TLR9, or STING, interact with EGFR and other protein tyrosine kinases and what are the functional consequences of their post-translational modifications. The article highlights an unexpected functional link between a growth factor receptor and cellular innate immune response.
期刊介绍:
Journal of Interferon & Cytokine Research (JICR) provides the latest groundbreaking research on all aspects of IFNs and cytokines. The Journal delivers current findings on emerging topics in this niche community, including the role of IFNs in the therapy of diseases such as multiple sclerosis, the understanding of the third class of IFNs, and the identification and function of IFN-inducible genes.