title: Suppression of apoptosis by v-ABL protein tyrosine kinase is associated with nuclear translocation and activation of protein kinase C in an interleukin-3-dependent haemopoietic cell line.
abstract: We previously demonstrated that activation of v-ABL protein tyrosine kinase resulted in suppression of apoptosis following interleukin-3 removal using an interleukin-3-dependent haemopoietic cell line transfected with a temperature-sensitive mutant of the v-abl oncoprotein (IC.DP). Cellular signalling events associated with the activation of v-ABL included increased levels of sn-1,2-diacylglycerol, an activator of protein kinase C. Calphostin C, a PKC inhibitor, restored apoptosis to interleukin-3-deprived IC.DP cells expressing active v-ABL. However, chronic exposure to the phorbol ester, 12-O-tetradecanoyl phorbol 13-acetate to downregulate protein kinase C did not attenuate the survival of IC.DP cells expressing active v-ABL. Translocation of a classical protein kinase C isozyme(s) to the nuclear fraction was observed 6 hours after activation of v-ABL, when nuclear protein kinase C activity was increased approximately 2-fold. The protein kinase C isozyme responsible, which was only partially downregulated by 12-O-tetradecanoyl phorbol 13-acetate, was identified as protein kinase C beta II. This translocation of protein kinase C beta II to the nucleus was inhibited by calphostin C. Taken together, these results suggest that nuclear translocation and activation of PKC beta II may play a role in v-ABL-mediated suppression of apoptosis.
authors.affiliation: Cancer Research Campaign Cellular and Molecular Pharmacology Group, School of Biological Sciences (G38), University of Manchester, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: Evans
authors.forename: J M
authors.initials: JM
authors.lastname: Lord
authors.forename: P J
authors.initials: PJ
authors.lastname: Owen-Lynch
authors.forename: G
authors.initials: G
authors.lastname: Johnson
authors.forename: C
authors.initials: C
authors.lastname: Dive
authors.forename: A D
authors.initials: AD
authors.lastname: Whetton
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016313:Genes, abl; D006412:Hematopoietic Stem Cells; D007377:Interleukin-3 / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007700:Kinetics; D009281:Naphthalenes / Q000494:pharmacology; D016374:Oncogene Proteins v-abl / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection
chemical_list: D004791:Enzyme Inhibitors; D007377:Interleukin-3; D007527:Isoenzymes; D009281:Naphthalenes; D016374:Oncogene Proteins v-abl; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate