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Cell Signal. 2009 Feb;21(2):309-16. doi: 10.1016/j.cellsig.2008.10.018. Epub 2008 Nov 5.

THOC5 couples M-CSF receptor signaling to transcription factor expression.

Author information

1
Stem Cell and Leukaemia Proteomics laboratory, Faculty of Medical and Human Sciences, University of Manchester, Christie Hospital, Wilmslow Road, Manchester M20 9BX, UK.

Abstract

THOC5 is a nuclear/cytoplasmic protein member of the spliceosome complex which potentiates C/EBP expression in adipocyte differentiation. As C/EBP family members are important regulators of myelopoiesis and THOC5 is highly expressed in neutrophil/macrophage progenitor cells we assessed the role of THOC5 in cytokine-stimulated monocytic development. M-CSF stimulated maturation of the NFS60 cell line was associated with enhanced THOC5 expression and phosphorylation. THOC5 was also shown to form a complex with C/EBPbeta. Ectopic expression of THOC5 mimicked M-CSF mediated cell maturation and enhanced protein expression of the myeloid transcription factors C/EBPbeta, C/EBPalpha, Pu-1 and also GAB2 (a PI-3 Kinase and macrophage development regulator). Increased THOC5 expression also mimicked M-CSF stimulated increases in the lipid second messenger PtdInsP(3). Inhibition of THOC5-induced increases in PtdInsP(3) levels abrogated the elevated levels of C/EBPbeta. Thus THOC5 expression can potentiate receptor signalling to transcription factor expression and monocyte differentiation.

PMID:
19015024
DOI:
10.1016/j.cellsig.2008.10.018
[Indexed for MEDLINE]

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