title: The Golgi-Associated Plant Pathogenesis-Related Protein GAPR-1 Enhances Type I Interferon Signaling Pathway in Response to Toll-Like Receptor 4.
abstract: Lipopolysaccharide (LPS) activates Toll-like receptor 4 (TLR4) through the TIRAP-MyD88 dependent and TRAM-TRIF dependent signaling pathways, respectively. However, the underlying relevance between two signaling pathways remains largely elusive. Here, we investigated the role of the Golgi-Associated plant Pathogenesis-Related protein (GAPR-1) in type I interferon (IFN) signaling pathway in response to TLR4. We found that TIRAP-MyD88 dependent kinase IRAK1 phosphorylated GAPR-1 at Serine 58 site. The phosphorylation of GAPR-1 promoted its interaction with TRAM-TRIF dependent inhibitor TMED7, and impaired TMED7-mediated disruption of the TRAM-TRIF complex to trigger IFN-β and the IL10 secretion. Collectively, our study identified a previously unrecognized role for GAPR-1 to control a unifying TLR4 signaling complex and to regulate type I IFN signaling activation. Understanding the mechanism of GAPR-1 in type I IFN signaling pathway would provide strategies for treatment of infectious diseases.
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, 518039, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116044, China. haolu19860813@126.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Hao
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, 518039, China. pony8980@163.com.
authors.forename: Weiren
authors.initials: W
authors.lastname: Huang
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, 518039, China. caizhiming2000@163.com.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Cai
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D016899:Interferon-beta / Q000276:immunology* / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D010766:Phosphorylation; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C458481:GLIPR2 protein, human; C508609:IL10 protein, human; D008070:Lipopolysaccharides; C507779:MYD88 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D053594:Myeloid Differentiation Factor 88; D017472:Receptors, Interleukin-1; C470409:TICAM1 protein, human; C434984:TIRAP protein, human; C495345:TLR4 protein, human; C574004:TMED7 protein, human; C486174:TRAM1 protein, human; D051197:Toll-Like Receptor 4; D033921:Vesicular Transport Proteins; D016753:Interleukin-10; D016899:Interferon-beta; C507768:IRAK1 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases
keywords: GAPR-1; innate immune; kinase phosphorylation; toll-like receptor 4; type I IFN