PKC mediates 12(S)‐HETE‐induced cytoskeletal rearrangement in B16A melanoma cells

J. Timar, D. Tang, R. Bazaz, M. M. Haddad, V. A. Kimler, J. D. Taylor, K. V. Honn

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46 Citations (Scopus)


The fatty acid 12(S)‐HETE may be a new second messenger capable of activating PKC. In tumor cells 12(S)‐HETE stimulates cytoskeleton‐dependent cellular responses such as adhesion and spreading. Analysis of 12(S)‐HETE effects on B16a melanoma cell cytoskeleton revealed reversible rearrangement of microtubules, microfilaments, the actin‐binding proteins, vinculin, myosin heavy (MHC) and light chains (MLC), as well as bundling of vimentin intermediate filaments. The alterations in microfilaments and intermediate filaments occurred very rapidly, i.e., 5 min after exposure of tumor cells to 12(S)‐HETE. The 12(S)‐HETE‐induced cytoskeletal alterations were accompanied by centrifugal organelle‐translocation. Interestingly, MLC exhibited clear association with the cytoplasmic organelles. Biochemical analysis of the 12(S)‐HETE effect indicated a PKC‐mediated reversible hyperphosphorylation of MLC, vimentin, and a 130 kD cytoskeletal‐associated protein. Optimal effects were obtained after 5 min treatment with 12(S)‐HETE at 0.1 μM concentration. 12(S)‐HETE pretreatment induced tumor cell spreading on a fibronectin matrix which required the intactness of all three major cytoskeletal components. The spreading process was dependent upon the activity of PKC. Our data suggest that 12(S)‐HETE is a physiological stimulant of PKC. Further, it induces rearrangement of the cytoskeleton of tumor cells in interphase resulting in the stimulation of cytoskeleton‐dependent cell activity such as spreading. © 1993 Wiley‐Liss, Inc.

Original languageEnglish
Pages (from-to)49-65
Number of pages17
JournalCell Motility and the Cytoskeleton
Issue number1
Publication statusPublished - 1993


  • MHC
  • MLC
  • fatty acid

ASJC Scopus subject areas

  • Structural Biology
  • Cell Biology

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