Identification of a novel taxol-sensitive kinase activity associated with the cytoskeleton.
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.
Wang
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Y
Department of Pharmaceutical Sciences, University of Southern California School of Pharmacy, Los Angeles, California, 90033, USA.
Duncan
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Ann
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DK
Hamm-Alvarez
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SF
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000201:enzymology* / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000302:isolation & purification* / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D011233:Precipitin Tests; D015398:Signal Transduction / Q000502:physiology; D014404:Tubulin / Q000276:immunology / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D014404:Tubulin; D020928:Mitogen-Activated Protein Kinases; D017239:Paclitaxel