| Autor: |
Pierce A; Stem Cell and Leukaemia Proteomics Laboratory, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK., Carney L, Hamza HG, Griffiths JR, Zhang L, Whetton BA, Gonzalez Sanchez MB, Tamura T, Sternberg D, Whetton AD |
| Jazyk: |
angličtina |
| Zdroj: |
British journal of haematology [Br J Haematol] 2008 May; Vol. 141 (5), pp. 641-50. Date of Electronic Publication: 2008 Mar 27. |
| DOI: |
10.1111/j.1365-2141.2008.07090.x |
| Abstrakt: |
The fusion protein TEL/PDGFRB is associated with chronic myelomonocytic leukaemia and has intrinsic tyrosine kinase activity. The effects of TEL/PDGFRB were assessed using the multipotent haemopoietic cell line FDCP-Mix. In the absence of growth factors, TEL/PDGFRB expression increased survival that was associated with elevated levels of phosphatidylinositol 3,4,5 trisphosphate (PIP3). Whilst TEL/PDGFRB had subtle effects on the growth factor requirements it had a profound effect on differentiation. The cells became refractory to cytokine-stimulated development, showing limited maturation but failing to produce fully mature cells. We have previously identified the spliceosome protein THOC5 as a target in macrophage colony-stimulating factor signalling and a protein involved in the regulation of transcription factor expression. TEL/PDGFRB expression increased the expression and phosphorylation of THOC5. Elevated expression of THOC5 increased PIP3 levels and decreased apoptosis. Mass spectrometry was used to identify a site for TEL/PDGFRB-mediated phosphorylation on THOC5, which was shown to be a target for a number of other leukaemogenic tyrosine kinases. Thus, THOC5 is a novel target for modulation of signal transduction with a potential role in leukaemogenesis. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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