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

Qing Zhou; Lu Hao; Weiren Huang; Zhiming Cai

doi:10.1007/s10753-015-0297-8

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

Inflammation. 2016 Apr;39(2):706-17. doi: 10.1007/s10753-015-0297-8.

Authors

Qing Zhou¹, Lu Hao², Weiren Huang³, Zhiming Cai⁴

Affiliations

¹ Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, 518039, China.
² Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116044, China. haolu19860813@126.com.
³ Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, 518039, China. pony8980@163.com.
⁴ Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, 518039, China. caizhiming2000@163.com.

PMID: 26678074
DOI: 10.1007/s10753-015-0297-8

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.

Keywords: GAPR-1; innate immune; kinase phosphorylation; toll-like receptor 4; type I IFN.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Vesicular Transport / metabolism
Cell Line
Enzyme Activation / immunology
HEK293 Cells
Humans
Immunity, Innate / immunology*
Interferon-beta / immunology*
Interferon-beta / metabolism
Interleukin-1 Receptor-Associated Kinases / metabolism
Interleukin-10 / immunology*
Interleukin-10 / metabolism
Lipopolysaccharides
Membrane Glycoproteins / metabolism
Membrane Proteins / metabolism*
Membrane Transport Proteins / metabolism
Myeloid Differentiation Factor 88 / metabolism
Phosphorylation
Receptors, Interleukin-1 / metabolism
Signal Transduction / immunology
Toll-Like Receptor 4 / immunology*
Vesicular Transport Proteins / metabolism

Substances

Adaptor Proteins, Vesicular Transport
GLIPR2 protein, human
IL10 protein, human
Lipopolysaccharides
MYD88 protein, human
Membrane Glycoproteins
Membrane Proteins
Membrane Transport Proteins
Myeloid Differentiation Factor 88
Receptors, Interleukin-1
TICAM1 protein, human
TIRAP protein, human
TLR4 protein, human
TMED7 protein, human
TRAM1 protein, human
Toll-Like Receptor 4
Vesicular Transport Proteins
Interleukin-10
Interferon-beta
IRAK1 protein, human
Interleukin-1 Receptor-Associated Kinases