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THOC5 couples M-CSF receptor signaling to transcription factor expression.
Carney L, Pierce A, Rijnen M, Gonzalez Sanchez M, Hamzah H, Zhang L, Tamura T, Whetton A
Cell Signal. 2009;21( 2).
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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.
Keyword(s)
Animals; Cell Line; Humans; Mice; Phosphorylation; Signal Transduction; Transfection; cytology: Monocytes; genetics: Transcription Factors; immunology: Nuclear Proteins; metabolism: 1-Phosphatidylinositol 3-Kinase; metabolism: CCAAT-Enhancer-Binding Protein-beta; metabolism: Macrophage Colony-Stimulating Factor; metabolism: Receptor, Macrophage Colony-Stimulating Factor