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

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Author

  • Charlotte E. Edling
  • Malin Pedersen
  • Leif Carlsson
  • Lars Rönnstrand
  • Ruth H. Palmer
  • Bengt Hallberg

Summary, in English

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.

Publishing year

2007

Language

English

Pages

260-268

Publication/Series

British Journal of Haematology

Volume

136

Issue

2

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Hematology

Keywords

  • Akt
  • protein kinase B
  • haematopoietic stem cells
  • protein kinase C
  • receptor tyrosine kinase c-Kit

Status

Published

ISBN/ISSN/Other

  • ISSN: 0007-1048