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.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Evans CA,Lord JM,Owen-Lynch PJ,Johnson G,Dive C,Whetton AD

subject

Has Abstract

pub_date

1995-07-01 00:00:00

pages

2591-8

eissn

0021-9533

issn

1477-9137

journal_volume

108 ( Pt 7)

pub_type

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