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

Caroline A. Evans, J. M. Lord, P. J. Owen-Lynch, G. Johnson, C. Dive, A. D. Whetton

Research output: Contribution to journalArticle

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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 β(II). This translocation of protein kinase C β(II) to the nucleus was inhibited by calphostin C. Taken together, these results suggest that nuclear translocation and activation of PKCβ(II) may play a role in v-ABL-mediated suppression of apoptosis.
Original languageEnglish
Pages (from-to)2591-2598
Number of pages8
JournalJournal of Cell Science
Volume108
Issue number7
Publication statusPublished - 1 Jul 1995
Externally publishedYes

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Interleukin-3
Protein-Tyrosine Kinases
Protein Kinase C
Apoptosis
Cell Line
Tetradecanoylphorbol Acetate
Isoenzymes
Down-Regulation
Oncogene Proteins
Phorbol Esters
Nuclear Proteins
Temperature

Cite this

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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 β(II). This translocation of protein kinase C β(II) to the nucleus was inhibited by calphostin C. Taken together, these results suggest that nuclear translocation and activation of PKCβ(II) may play a role in v-ABL-mediated suppression of apoptosis.",
keywords = "Apoptosis, Haemopoietic cell line, Interleukin-3 withdrawal, Protein kinase C, Survival signal, v-ABL",
author = "Evans, {Caroline A.} and Lord, {J. M.} and Owen-Lynch, {P. J.} and G. Johnson and C. Dive and Whetton, {A. D.}",
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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. / Evans, Caroline A.; Lord, J. M.; Owen-Lynch, P. J.; Johnson, G.; Dive, C.; Whetton, A. D.

In: Journal of Cell Science, Vol. 108, No. 7, 01.07.1995, p. 2591-2598.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Evans, Caroline A.

AU - Lord, J. M.

AU - Owen-Lynch, P. J.

AU - Johnson, G.

AU - Dive, C.

AU - Whetton, A. D.

PY - 1995/7/1

Y1 - 1995/7/1

N2 - 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 β(II). This translocation of protein kinase C β(II) to the nucleus was inhibited by calphostin C. Taken together, these results suggest that nuclear translocation and activation of PKCβ(II) may play a role in v-ABL-mediated suppression of apoptosis.

AB - 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 β(II). This translocation of protein kinase C β(II) to the nucleus was inhibited by calphostin C. Taken together, these results suggest that nuclear translocation and activation of PKCβ(II) may play a role in v-ABL-mediated suppression of apoptosis.

KW - Apoptosis

KW - Haemopoietic cell line

KW - Interleukin-3 withdrawal

KW - Protein kinase C

KW - Survival signal

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M3 - Article

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JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

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ER -