The Golgi-Associated Plant Pathogenesis-Related Protein GAPR-1 Enhances Type I Interferon Signaling Pathway in Response to Toll-Like Receptor 4.

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.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}