| First Author | Miyake A | Year | 2008 |
| Journal | Genes Cells | Volume | 13 |
| Issue | 2 | Pages | 209-19 |
| PubMed ID | 18233962 | Mgi Jnum | J:138255 |
| Mgi Id | MGI:3804612 | Doi | 10.1111/j.1365-2443.2007.01161.x |
| Citation | Miyake A, et al. (2008) Negative regulation by SHPS-1 of Toll-like receptor-dependent proinflammatory cytokine production in macrophages. Genes Cells 13(2):209-19 |
| abstractText | 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-alpha (TNF-alpha) 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-kappaB. 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-kappaB-dependent signaling. |
