Downregulation of cell-to-cell communication by the viral src gene is blocked by TMB-8 and recovery of communication is blocked by vanadate.
The viral src gene downregulates junctional communication, closing cell-to-cell membrane channels presumably by way of the phosphoinositide signal route. We show that TMB-8 [8-N, N-(diethylamino) octyl-3,4,5-trimethoxybenzoate] counteracts this downregulation in cells transformed by temperature-sensitive mutant Rous sarcoma virus: TMB-8 (36-72 microM) raises junctional permeability when applied during activity of src protein kinase, i.e., at steady permissive temperature; and TMB-8 inhibits the fall of junctional permeability, when the activity of src protein kinase gets turned on. TMB-8 also (reversibly) inhibits the growth of the cells at permissive temperature and reverses the morphological changes associated with transformation. The morphological reversal lags several hours behind the junctional-permeability reversal. Communication recovers within a few minutes when the activity of the src protein kinase is turned off (in absence of TMB-8). Sodium orthovanadate (20 microM) prevents this recovery, but it has no major effect on junctional permeability on its own. We discuss possible modes of action of these agents on critical stages of the signal route, related to intracellular Ca2+ and protein kinase C.
D000818:Animals; D001358:Avian Sarcoma Viruses / Q000235:genetics; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D004625:Embryo, Nonmammalian; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005796:Genes; D005814:Genes, Viral; D007365:Intercellular Junctions / Q000187:drug effects; D051379:Mice; D015688:Oncogene Protein pp60(v-src); D011494:Protein Kinases / Q000235:genetics; D011784:Quail; D012191:Retroviridae Proteins / Q000235:genetics*; D014638:Vanadates; D014639:Vanadium / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D012191:Retroviridae Proteins; D014639:Vanadium; D014638:Vanadates; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D011494:Protein Kinases; D015688:Oncogene Protein pp60(v-src)