Related resources
Full-text held externally
Search for item elsewhere
University researcher(s)
Academic department(s)
THOC5 spliceosome protein: a target for leukaemogenic tyrosine kinases that affects inositol lipid turnover.
Pierce, A, Carney, L, Hamza, H, Griffiths, J, Zhang, L, Whetton, B, Gonzalez Sanchez, M, Tamura, T, Sternberg, D, Whetton, A
Br J Haematol. 2008;141( 5).
Access to files
Full-text and supplementary files are not available from Manchester eScholar. Full-text is available externally using the following links:
Full-text held externally
Abstract
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.
Keyword(s)
Cell Line; Humans; Phosphorylation; cytology: Hematopoietic Stem Cells; drug effects: Cell Differentiation; metabolism: Inositol; metabolism: Nuclear Proteins; metabolism: Oncogene Proteins, Fusion; metabolism: Phosphatidylinositol Phosphates; pharmacology: Growth Substances; physiology: Apoptosis; physiology: Cell Survival; physiology: Signal Transduction