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Separation of zinc-dependent and zinc-independent events during early LPS-stimulated TLR4 signaling in macrophage cells
Authors:Ying Wan  Michael J. Petris  Scott C. Peck
Affiliation:1. Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA;2. Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USA;3. Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA
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.
Keywords:Zinc   LPS   Macrophage   Signaling   Proteasome-independent degradation
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