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Negative regulation by SHPS-1 of Toll-like receptor-dependent proinflammatory cytokine production in macrophages.
- Source :
- Genes to Cells; Feb2008, Vol. 13 Issue 2, p209-219, 11p, 2 Black and White Photographs, 5 Graphs
- Publication Year :
- 2008
-
Abstract
- SHPS-1 is a transmembrane protein predominantly expressed in macrophages. The possible role of SHPS-1 in regulation of Toll-like receptor (TLR)-dependent production of proinflammatory cytokines by macrophages has remained unknown, however. We now show that expression either of a mutant version of mouse SHPS-1 (SHPS-1–4F) in which the four tyrosine phosphorylation sites in the cytoplasmic region are replaced by phenylalanine or of a chimeric protein comprising the extracellular and transmembrane regions of human CD8 fused to the cytoplasmic region of SHPS-1–4F (CD8–4F) markedly promoted the production of tumor necrosis factor-α (TNF-α) or interleukin-6 (IL-6) induced by lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid [poly(I : C)] in RAW264.7 macrophages. In contrast, expression of a mutant form of SHPS-1 that lacks most of the cytoplasmic region did not promote such responses. Expression of SHPS-1–4F promoted the LPS- or poly(I : C)-induced activation of NF-κB. LPS and poly(I : C) each induced the tyrosine phosphorylation of SHPS-1 through a Src family kinase and the association of SHPS-1 with SHP-1 and SHP-2. These results suggest that LPS or poly(I : C) induces tyrosine phosphorylation of SHPS-1 and the association of SHPS-1 with SHP-1 and SHP-2 in a manner dependent on a Src family kinase. SHPS-1 then negatively regulates TLR4- or TLR3-dependent cytokine production through inhibition of NF-κB-dependent signaling. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 13569597
- Volume :
- 13
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Genes to Cells
- Publication Type :
- Academic Journal
- Accession number :
- 28625817
- Full Text :
- https://doi.org/10.1111/j.1365-2443.2007.01161.x