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Haematopoietic progenitor cells utilise conventional PKC to suppress PKB/Akt activity in response to c-Kit stimulation

Edling, Charlotte E.; Pedersen, Malin LU ; Carlsson, Leif; Rönnstrand, Lars LU ; Palmer, Ruth H. and Hallberg, Bengt (2007) In British Journal of Haematology 136(2). p.260-268
Abstract
Receptor tyrosine kinase (RTK) c-Kit signalling is crucial for the proliferation, survival and differentiation of haematopoietic stem cells (HSCs). To further understand the mechanisms underlying these events we explored how the downstream mediators interact. The present study investigated the function of conventional protein kinase Cs (c-PKC) in c-Kit mediated signalling pathways in HSC-like cell lines. This analysis supported earlier findings, that steel factor (SF) activates c-PKC, extracellular signal-regulated kinase (Erk) and protein kinase B (PKB). The present results were consistent with an important role of c-PKC in the positive activation of Erk and for proliferation. Further, it was observed that c-PKC negatively regulated PKB... (More)
Receptor tyrosine kinase (RTK) c-Kit signalling is crucial for the proliferation, survival and differentiation of haematopoietic stem cells (HSCs). To further understand the mechanisms underlying these events we explored how the downstream mediators interact. The present study investigated the function of conventional protein kinase Cs (c-PKC) in c-Kit mediated signalling pathways in HSC-like cell lines. This analysis supported earlier findings, that steel factor (SF) activates c-PKC, extracellular signal-regulated kinase (Erk) and protein kinase B (PKB). The present results were consistent with an important role of c-PKC in the positive activation of Erk and for proliferation. Further, it was observed that c-PKC negatively regulated PKB activity upon SF stimulation, indicating that c-PKC acts as a suppressor of c-Kit signalling. Finally, these observations were extended to show that c-PKC mediated the phosphorylation of the endogenous c-Kit receptor on serine 746, resulting in decreased overall tyrosine phosphorylation of c-Kit upon SF stimulation. This report showed that this specific feedback mechanism of c-PKC mediated phosphorylation of the c-Kit receptor has consequences for both proliferation and survival of HSC-like cell lines. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Akt, protein kinase B, haematopoietic stem cells, protein kinase C, receptor tyrosine kinase c-Kit
in
British Journal of Haematology
volume
136
issue
2
pages
260 - 268
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000243298200009
  • scopus:33845874383
ISSN
0007-1048
DOI
10.1111/j.1365-2141.2006.06434.x
language
English
LU publication?
yes
id
4df455cd-bedc-4af0-9f4d-7adb65d03510 (old id 679538)
date added to LUP
2007-12-06 11:37:40
date last changed
2017-01-01 05:18:02
@article{4df455cd-bedc-4af0-9f4d-7adb65d03510,
  abstract     = {Receptor tyrosine kinase (RTK) c-Kit signalling is crucial for the proliferation, survival and differentiation of haematopoietic stem cells (HSCs). To further understand the mechanisms underlying these events we explored how the downstream mediators interact. The present study investigated the function of conventional protein kinase Cs (c-PKC) in c-Kit mediated signalling pathways in HSC-like cell lines. This analysis supported earlier findings, that steel factor (SF) activates c-PKC, extracellular signal-regulated kinase (Erk) and protein kinase B (PKB). The present results were consistent with an important role of c-PKC in the positive activation of Erk and for proliferation. Further, it was observed that c-PKC negatively regulated PKB activity upon SF stimulation, indicating that c-PKC acts as a suppressor of c-Kit signalling. Finally, these observations were extended to show that c-PKC mediated the phosphorylation of the endogenous c-Kit receptor on serine 746, resulting in decreased overall tyrosine phosphorylation of c-Kit upon SF stimulation. This report showed that this specific feedback mechanism of c-PKC mediated phosphorylation of the c-Kit receptor has consequences for both proliferation and survival of HSC-like cell lines.},
  author       = {Edling, Charlotte E. and Pedersen, Malin and Carlsson, Leif and Rönnstrand, Lars and Palmer, Ruth H. and Hallberg, Bengt},
  issn         = {0007-1048},
  keyword      = {Akt,protein kinase B,haematopoietic stem cells,protein kinase C,receptor tyrosine kinase c-Kit},
  language     = {eng},
  number       = {2},
  pages        = {260--268},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {British Journal of Haematology},
  title        = {Haematopoietic progenitor cells utilise conventional PKC to suppress PKB/Akt activity in response to c-Kit stimulation},
  url          = {http://dx.doi.org/10.1111/j.1365-2141.2006.06434.x},
  volume       = {136},
  year         = {2007},
}