Document Detail

Cytoskeletal active drugs modulate signal transduction in the protein kinase C pathway.
MedLine Citation:
PMID:  8242794     Owner:  NLM     Status:  MEDLINE    
The cytoskeletal network of cells is postulated to play a role in the signal transduction pathways of growth promoting stimuli. We show here that cytoskeletal active drugs modulate the mitogenic signal transduction pathway of the tumor promoter TPA in 3T3-L1 cells. Compounds which act on microtubules (vinblastine sulfate) and microfilaments (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 mRNA levels 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.
G K Pavlath; Y Shimizu; N Shimizu
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cell structure and function     Volume:  18     ISSN:  0386-7196     ISO Abbreviation:  Cell Struct. Funct.     Publication Date:  1993 Jun 
Date Detail:
Created Date:  1994-01-06     Completed Date:  1994-01-06     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7608465     Medline TA:  Cell Struct Funct     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  151-60     Citation Subset:  IM    
Department of Molecular and Cellular Biology, University of Arizona, Tucson 85721.
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MeSH Terms
3T3 Cells
Cytochalasin B / pharmacology
Cytoskeleton / physiology*
DNA / biosynthesis*,  drug effects,  genetics
Protein Kinase C / drug effects,  physiology*
Signal Transduction / drug effects,  physiology*
Tetradecanoylphorbol Acetate / pharmacology
Vinblastine / pharmacology
Grant Support
Reg. No./Substance:
14930-96-2/Cytochalasin B; 16561-29-8/Tetradecanoylphorbol Acetate; 865-21-4/Vinblastine; 9007-49-2/DNA; EC Kinase C

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