Lancaster EPrints

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

Xenaki, Dia and Pierce, Andrew and Underhill-Day, Nick and Whetton, Anthony D. and Owen-Lynch, P. Jane (2004) Bcr-Abl-mediated molecular mechanism for apoptotic suppression in multipotent haemopoietic cells: a role for PKCβII. Cellular Signalling, 16 (2). pp. 145-156. ISSN 0898-6568

Full text not available from this repository.

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activated PKCβII in haemopoietic progenitor FDCP-Mix cells stimulates enhanced cell survival when IL-3 is withdrawn.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.

Item Type: Article
Journal or Publication Title: Cellular Signalling
Uncontrolled Keywords: Bcr-Abl ; Cell survival ; Protein kinase CβII ; ERK ; STAT-5b ; Chronic myeloid leukaemia
Subjects: Q Science > QH Natural history > QH301 Biology
Departments: Faculty of Health and Medicine > Biomedical & Life Sciences
ID Code: 9253
Deposited By: Dr P Jane Owen-Lynch
Deposited On: 03 Jun 2008 09:57
Refereed?: Yes
Published?: Published
Last Modified: 26 Jul 2012 18:34
Identification Number:
URI: http://eprints.lancs.ac.uk/id/eprint/9253

Actions (login required)

View Item