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Updated: Aug 22, 2026

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
GPLD1-mediated regulation of the type I interferon-induced signaling pathway and antiviral activity
Qian Zhao1, Renxia Zhang2, Yukang Yuan3
1Department of Clinical Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, 242 Guangji Rd, Suzhou, Jiangsu 215008, China; International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu, 215123, China.
Abstract:
Glycosylphosphatidylinositol-specific phospholipase D1 (GPLD1) is traditionally known as a secreted enzyme that sheds glycosylphosphatidylinositol (GPI)-anchored proteins. Emerging evidence suggests its involvement in immune modulation. In this study, we report a non-canonical intracellular function of GPLD1 in potentiating IFN-I-mediated antiviral signaling. Mechanistically, GPLD1 physically interacts with signal transducer and activator of transcription 2 (STAT2) and competitively blocks its interaction with protein-tyrosine phosphatase 1B (PTP1B), a bona fide phosphatase that directly dephosphorylates STAT2 at Tyr690. By shielding STAT2 from PTP1B-mediated dephosphorylation, GPLD1 sustains STAT2 phosphorylation and facilitates time-dependent STAT2 nuclear translocation, thereby amplifying interferon-stimulated gene (ISG) expression and antiviral responses. Collectively, we identify a novel molecular mechanism by which GPLD1 regulates the IFN-I signaling pathway, providing a potential therapeutic target for the development of future antiviral strategies.
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