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

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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 et al.
In: Cellular Signalling, Vol. 16, No. 2, 02.2004, p. 145-156.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Xenaki, D, Pierce, A, Underhill-Day, N, Whetton, AD & Owen-Lynch, PJ 2004, 'Bcr-Abl-mediated molecular mechanism for apoptotic suppression in multipotent haemopoietic cells: a role for PKCβII.', Cellular Signalling, vol. 16, no. 2, pp. 145-156. https://doi.org/10.1016/S0898-6568(03)00101-3

APA

Xenaki, D., Pierce, A., Underhill-Day, N., Whetton, A. D., & Owen-Lynch, P. J. (2004). Bcr-Abl-mediated molecular mechanism for apoptotic suppression in multipotent haemopoietic cells: a role for PKCβII. Cellular Signalling, 16(2), 145-156. https://doi.org/10.1016/S0898-6568(03)00101-3

Vancouver

Xenaki D, Pierce A, Underhill-Day N, Whetton AD, Owen-Lynch PJ. Bcr-Abl-mediated molecular mechanism for apoptotic suppression in multipotent haemopoietic cells: a role for PKCβII. Cellular Signalling. 2004 Feb;16(2):145-156. doi: 10.1016/S0898-6568(03)00101-3

Author

Xenaki, Dia ; Pierce, Andrew ; Underhill-Day, Nick et al. / 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.

Bibtex

@article{c15630da5cb14f388e0880b94c28f291,
title = "Bcr-Abl-mediated molecular mechanism for apoptotic suppression in multipotent haemopoietic cells: a role for PKCβII.",
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.",
keywords = "Bcr-Abl, Cell survival, Protein kinase CβII, ERK, STAT-5b, Chronic myeloid leukaemia",
author = "Dia Xenaki and Andrew Pierce and Nick Underhill-Day and Whetton, {Anthony D.} and Owen-Lynch, {P. Jane}",
year = "2004",
month = feb,
doi = "10.1016/S0898-6568(03)00101-3",
language = "English",
volume = "16",
pages = "145--156",
journal = "Cellular Signalling",
issn = "0898-6568",
publisher = "Elsevier Inc.",
number = "2",

}

RIS

TY - JOUR

T1 - Bcr-Abl-mediated molecular mechanism for apoptotic suppression in multipotent haemopoietic cells: a role for PKCβII.

AU - Xenaki, Dia

AU - Pierce, Andrew

AU - Underhill-Day, Nick

AU - Whetton, Anthony D.

AU - Owen-Lynch, P. Jane

PY - 2004/2

Y1 - 2004/2

N2 - 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.

AB - 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.

KW - Bcr-Abl

KW - Cell survival

KW - Protein kinase CβII

KW - ERK

KW - STAT-5b

KW - Chronic myeloid leukaemia

U2 - 10.1016/S0898-6568(03)00101-3

DO - 10.1016/S0898-6568(03)00101-3

M3 - Journal article

VL - 16

SP - 145

EP - 156

JO - Cellular Signalling

JF - Cellular Signalling

SN - 0898-6568

IS - 2

ER -