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© The Rockefeller University Press, 0021-9525/2000//1207 $5.00
The Journal of Cell Biology, Volume 149, Number 6, , 2000 1207-1214

Tumor Necrosis Factor Induces Hyperphosphorylation of Kinesin Light Chain and Inhibits Kinesin-Mediated Transport of Mitochondria

^a Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology and Ghent University, B-9000 Ghent, Belgium
^b Cell Biology Program, European Molecular Biology Laboratory, D-69012 Heidelberg, Germany
^c Max-Planck Institute for Cell Biology and Genetics, D-01307 Dresden, Germany
Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology and Ghent University, K. L. Ledeganckstraat 35, B-9000 Ghent, Belgium.32 9 264 534832 9 264 5310

johan.grooten{at}dmb.rug.ac.be

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.

Key Words: microtubule • organelle • okadaic acid • mitogen-activated protein kinase • phosphorylation

© 2000 The Rockefeller University Press

Abbreviations used in this paper: 2-DE, two-dimensional gel electrophoresis; Ab, antibody; KHC, kinesin heavy chain; KLC, kinesin light chain; MAP, microtubule-associated protein; MAPK, mitogen-activated protein kinase; MT, microtubule; OA, okadaic acid; PKA, protein kinase A; TNF, tumor necrosis factor.

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