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PMID: 10851018 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Tumor necrosis factor induces hyperphosphorylation of kinesin light chain and inhibits kinesin-mediated transport of mitochondria.

The Journal of cell biology ·Vol. 149 ·No. 6 ·2000-06-12 ·Pages 1207-14

De Vos K, Severin F, Van Herreweghe F, Vancompernolle K, Goossens V, Hyman A, Grooten J

Abstract

The molecular motor kinesin is an ATPase that mediates plus end-directed transport of organelles along microtubules. Although the biochemical properties of kinesin are extensively studied, conclusive data on regulation of kinesin-mediated transport are largely lacking. Previously, we showed that the proinflammatory cytokine tumor necrosis factor induces perinuclear clustering of mitochondria. Here, we show that tumor necrosis factor impairs kinesin motor activity and hyperphosphorylates kinesin light chain through activation of two putative kinesin light chain kinases. Inactivation of kinesin, hyperphosphorylation of kinesin light chain, and perinuclear clustering of mitochondria exhibit the same p38 mitogen-activated kinase dependence, indicating their functional relationship. These data provide evidence for direct regulation of kinesin-mediated organelle transport by extracellular stimuli via cytokine receptor signaling pathways.

MeSH Terms
Animals Cell Line Enzyme Activation Enzyme Inhibitors/pharmacology Imidazoles/pharmacology Kinesins/metabolism Microtubule-Associated Proteins/metabolism Microtubules/metabolism Mitochondria/metabolism Mitogen-Activated Protein Kinases/metabolism Molecular Motor Proteins/metabolism Phosphorylation Pyridines/pharmacology Receptors, Tumor Necrosis Factor/metabolism Signal Transduction Tumor Necrosis Factor-alpha/pharmacology p38 Mitogen-Activated Protein Kinases
Chemicals
Enzyme Inhibitors Imidazoles Microtubule-Associated Proteins Molecular Motor Proteins Pyridines Receptors, Tumor Necrosis Factor Tumor Necrosis Factor-alpha Mitogen-Activated Protein Kinases p38 Mitogen-Activated Protein Kinases Kinesins SB 203580
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
De Vos K
Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology and Ghent University, B-9000 Ghent, Belgium.
Severin F
Van Herreweghe F
Vancompernolle K
Goossens V
Hyman A
Grooten J
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40 references, click to expand
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.149.6.1207
Published
2000-06-12
Pages
1207-14
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2175118
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.149.6.1207 PMC Full Text View journal details
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