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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Charlotte E. Edling
  • Malin Pedersen
  • Leif Carlsson
  • Lars Rönnstrand
  • Ruth H. Palmer
  • Bengt Hallberg
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology

Keywords

  • Akt, protein kinase B, haematopoietic stem cells, protein kinase C, receptor tyrosine kinase c-Kit
Original languageEnglish
Pages (from-to)260-268
JournalBritish Journal of Haematology
Volume136
Issue number2
Publication statusPublished - 2007
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Experimental Clinical Chemistry (013016010)