Bcr-Abl-mediated molecular mechanism for apoptotic suppression in multipotent haemopoietic cells: A role for PKCβII

Dia Xenaki, Andrew Pierce, Nick Underhill-Day, Anthony D. Whetton, P. Jane Owen-Lynch

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Bcr-Abl protein tyrosine kinase (PTK) activity is a feature of chronic myeloid leukaemia and confers a survival advantage on haemopoietic progenitor cells. We have expressed conditional mutant of the Bcr-Abl PTK in the FDCP-Mix A4 multipotent haematopoietic cell line in order to examine the molecular mechanisms whereby Bcr-Abl PTK leads to enhanced cell survival under conditions in which normal cells die. Activation of Bcr-Abl PTK does not phosphorylate or activate either ERK-1/2 or JAK-2/STAT-5b, suggesting that these signal transduction pathways are not involved in Abl PTK-mediated suppression of apoptosis in FDCP-Mix cells. However, protein kinase C (PKC) does have a role to play. Inhibition of PKC results in a reversal of Bcr-Abl PTK-mediated survival in the absence of growth factor and Bcr-Abl stimulates translocation of the PKCβII isoform to the nucleus. Furthermore, expression of a constitutively activated PKCβII in haemopoietic progenitor FDCP-Mix cells stimulates enhanced cell survival when IL-3 is withdrawn. However, expression of this constitutively activated PKC isoform does not suppress cytotoxic drug-induced apoptosis. Thus Bcr-Abl PTK has pleiotropic effects which can suppress cell death induced by a number of stimuli.

LanguageEnglish
Pages145-156
Number of pages12
JournalCellular Signalling
Volume16
Issue number2
DOIs
Publication statusPublished - 1 Feb 2004
Externally publishedYes

Fingerprint

bcr-abl Fusion Proteins
Protein-Tyrosine Kinases
Protein Kinase C
Cell Survival
Protein Isoforms
Apoptosis
Interleukin-3
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Signal Transduction
Intercellular Signaling Peptides and Proteins
Cell Death
Stem Cells
Cell Line
Pharmaceutical Preparations

Cite this

Xenaki, Dia ; Pierce, Andrew ; Underhill-Day, Nick ; Whetton, Anthony D. ; Owen-Lynch, P. Jane. / Bcr-Abl-mediated molecular mechanism for apoptotic suppression in multipotent haemopoietic cells : A role for PKCβII. In: Cellular Signalling. 2004 ; Vol. 16, No. 2. pp. 145-156.
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Bcr-Abl-mediated molecular mechanism for apoptotic suppression in multipotent haemopoietic cells : A role for PKCβII. / Xenaki, Dia; Pierce, Andrew; Underhill-Day, Nick; Whetton, Anthony D.; Owen-Lynch, P. Jane.

In: Cellular Signalling, Vol. 16, No. 2, 01.02.2004, p. 145-156.

Research output: Contribution to journalArticle

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