Separation of zinc‐dependent and zinc‐independent events during early LPS‐stimulated TLR4 signaling in macrophage cells. Issue 17 (6th June 2014)

• Record Type: Journal Article
• Authors: Wan, Ying; Petris, Michael J.; Peck, Scott C.
• Is Part Of: FEBS letters. Volume 588:Issue 17(2014)
• Page Start: 2928
• Page End: 2935
• Publication Date: 2014-06-06
• Subjects: Zinc -- LPS -- Macrophage -- Signaling -- Proteasome-independent degradation; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2014.05.043
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Free zinc is required for proper lipopolysaccharide (LPS)‐stimulated signaling, but potential sites of action in the pathway have not been defined. In this work, we provide in vitro and ex vivo evidence that zinc is not required for phosphorylation or ubiquitylation of IRAK1, a kinase functioning early in the TLR4 pathway. However, degradation of ubiquitylated IRAK1 occurred via a zinc‐dependent, proteasome‐independent pathway. These results provide evidence of a novel site of action for zinc during TLR4‐mediated inflammatory responses. Abstract : Short‐term depletion of zinc blocks diverse LPS‐induced phosphorylation events. Zinc is not required for IRAK1 phosphorylation or ubiquitylation. Zinc is required for proteasome‐independent degradation of IRAK1.