| First Author | Hardin AO | Year | 2006 |
| Journal | Biochem Biophys Res Commun | Volume | 342 |
| Issue | 2 | Pages | 547-55 |
| PubMed ID | 16487932 | Mgi Jnum | J:106161 |
| Mgi Id | MGI:3617691 | Doi | 10.1016/j.bbrc.2006.02.005 |
| Citation | Hardin AO, et al. (2006) SHP-1 inhibits LPS-mediated TNF and iNOS production in murine macrophages. Biochem Biophys Res Commun 342(2):547-555 |
| abstractText | Several lines of evidence have suggested that protein tyrosine phosphatases, including CD45 and SHP-1, regulate macrophage activation. Macrophages from mice lacking SHP-1 (motheaten mice) are hyper-responsive to many stimuli, suggesting that SHP-1 may negatively regulate macrophage activation. Herein we report that the repressible/inducible over-expression of wild-type SHP-1 in a subclone of RAW 264.7 macrophages (RAW-TT10 cells) inhibited both TNF secretion and iNOS protein accumulation in response to stimulation with lipopolysaccharide (LPS) and recombinant murine interferon-gamma and led to diminished LPS-mediated tyrosine phosphorylation of vav1. In contrast, expression of a truncated SHP-1 construct previously shown to interfere with endogenous SHP-1 function modestly augmented LPS-mediated TNF and iNOS production and did not inhibit vav1 tyrosine phosphorylation. Taken together, these data provide the first direct evidence that SHP-1 inhibits macrophage activation by LPS and suggest that this effect may be mediated in part by dephosphorylation of vav1. |
