| First Author | Zhu M | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 6 | Pages | 2733-41 |
| PubMed ID | 22308309 | Mgi Jnum | J:181866 |
| Mgi Id | MGI:5314294 | Doi | 10.4049/jimmunol.1101581 |
| Citation | Zhu M, et al. (2012) Tyrosine Phosphorylation-Independent Regulation of Lipopolysaccharide-Mediated Response by the Transmembrane Adaptor Protein LAB. J Immunol 188(6):2733-41 |
| abstractText | Linker for activation of B cells (LAB)/non-T cell activation linker is a transmembrane adaptor protein that functions in immunoreceptor-mediated signaling. Published studies have shown that LAB has both positive and negative roles in regulating TCR and high-affinity Fc receptor-mediated signaling and cellular function. In this study, we showed that LAB was also expressed in dendritic cells and that LAB deficiency affected LPS-mediated signaling and cytokine production. LPS-mediated MAPK activation was enhanced in LAB(-/-) bone marrow-derived dendritic cells. These bone marrow-derived dendritic cells also produced more TNF-alpha, IL-6, and IL-10 than wild-type cells. Moreover, LAB(-/-) mice were hyperresponsive to LPS-induced septic shock. These data indicated that LAB has a negative role in LPS-mediated responses. By using LAB knockin mice, which harbor mutations at five membrane-distal tyrosines, we further showed that, in contrast to its role in immunoreceptor-mediated signaling, LAB function in LPS-mediated signaling pathway did not depend on its tyrosine phosphorylation. Our study suggested a novel mechanism by which LAB functions in the regulation of innate immunity. |
