Journal
FEBS LETTERS
Volume 588, Issue 17, Pages 2928-2935Publisher
WILEY
DOI: 10.1016/j.febslet.2014.05.043
Keywords
Zinc; LPS; Macrophage; Signaling; Proteasome-independent degradation
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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. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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