Cell Structure and Function
Online ISSN : 1347-3700
Print ISSN : 0386-7196
ISSN-L : 0386-7196
Cytoskeletal Active Drugs Modulate Signal Transduction in the Protein Kinase C Pathway
Grace K. PavlathYoshiko ShimizuNobuyoshi Shimizu
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1993 Volume 18 Issue 3 Pages 151-160

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Abstract

The cytoskeletal network of cells is postulated to play a role in the signal transduction pathways of growth promoting stimuli. Weshow here that cytoskeletal active drugs modulate the mitogenic signal transduction pathway of the tumor promoter TPAin 3T3-L1 cells. Compounds which act on microtubules (vinblastine sulfate) and micro filaments (cytochalasin B) have opposite effects on DNA synthesis. Vinblastine sulfate leads to stimulation, whereas cytochalasin B causes potent inhibition of DNA synthesis in response to TPA. These drugs are cell cycle specific and apparently exert their regulatory action distal to activation of protein kinase C by TPA. The expression of four genes necessary for DNA synthesis in response to tumor promoters was examined: two nuclear proto-oncogenes (c-myc and c-fos), a transcription factor (c-jun/AP-1) and a key enzyme involved in polyamine synthesis (ornithine decarboxylase). c-jun mRNAlevels are not modulated during the action of cytoskeletal disrupting drugs on TPA-mediated mitogenesis, whereas c-myc and c-fos mRNA levels are similarly enhanced. Expression of ornithine decarboxylase mRNA and protein is increased by vinblastine sulfate but decreased by cytochalasin B in TPA treated cells. These data indicate that changes in cytoskeletal organization may play a role in regulating the levels of an enzyme critical for DNA synthesis.

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