SUPPRESSION OF APOPTOSIS BY V-ABL PROTEIN-TYROSINE KINASE IS ASSOCIATED WITH NUCLEAR TRANSLOCATION AND ACTIVATION OF PROTEIN-KINASE-C IN ANINTERLEUKIN-3-DEPENDENT HEMATOPOIETIC-CELL LINE

We previously demonstrated that activation of v-ABL protein tyrosine k inase resulted in suppression of apoptosis following interleukin-3 rem oval using an interleukin-3-dependent haemopoietic cell line transfect ed 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 pr otein kinase C, Calphostin C, a PKC inhibitor, restored apoptosis to i nterleukin-3-deprived IC.DP cells expressing active v-ABL, However, ch ronic exposure to the phorbol ester, 12-O-tetradecanoyl phorbol 13-ace tate to downregulate protein kinase C did not attenuate the survival o f IC.DP cells expressing active v-ABL, Translocation of a classical pr otein 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 protien kinase C isozyme responsi ble, which was only partially downregulated by 12-O-tetradecanoyl phor bol 13-acetate, was identified as protein kinase C beta(II). This tran slocation of protein kinase C beta(II) to the nucleus was inhibited by calphostin C. Taken together, these results suggest that nuclear tran slocation and activation of PKC beta(II) may play a role in v-ABL-medi ated suppression of apoptosis.