Identification of a novel taxol-sensitive kinase activity associated with the cytoskeleton

Biochem Biophys Res Commun. 2000 Nov 2;277(3):525-30. doi: 10.1006/bbrc.2000.3707.

Abstract

The microtubule-targeted drug, taxol, enhances assembly of alphabeta tubulin dimers into microtubules. Recent work has established that taxol also elicits diverse effects on intracellular signaling. In-gel kinase assays with myelin basic protein as substrate revealed that taxol treatment significantly (P </= 0.05) reduced the activity of a 55 kD kinase present in cytoskeletal extracts from CV-1 cells. In vitro phosphorylation of myelin basic protein by tubulin immunoprecipitates revealed a comparable activity, consistent with the association of this kinase activity with microtubules. This novel kinase activity was detected in the cytoskeletal fraction of several other cell types including 10T12 fibroblasts and PC-3 prostate carcinoma cells, but was not detected in cytoskeletal fractions from HeLa cells. This taxol-sensitive kinase activity may participate in conveying information about taxol-induced structural changes in microtubules to changes in intracellular signaling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Cells, Cultured
  • Chlorocebus aethiops
  • Cytoskeleton / enzymology*
  • Cytoskeleton / metabolism
  • Microtubules / drug effects
  • Microtubules / metabolism*
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / isolation & purification*
  • Mitogen-Activated Protein Kinases / metabolism
  • Paclitaxel / pharmacology*
  • Precipitin Tests
  • Signal Transduction / physiology
  • Tubulin / immunology
  • Tubulin / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Tubulin
  • Mitogen-Activated Protein Kinases
  • Paclitaxel