| First Author | Xiao W | Year | 2011 |
| Journal | Immunity | Volume | 34 |
| Issue | 6 | Pages | 893-904 |
| PubMed ID | 21683628 | Mgi Jnum | J:174006 |
| Mgi Id | MGI:5050772 | Doi | 10.1016/j.immuni.2011.04.010 |
| Citation | Xiao W, et al. (2011) Phospholipase C-beta3 Regulates FcvarepsilonRI-Mediated Mast Cell Activation by Recruiting the Protein Phosphatase SHP-1. Immunity 34(6):893-904 |
| abstractText | Mast cells are major effectors in high-affinity IgE receptor (FcvarepsilonRI)-dependent allergic reactions. Here we show that phospholipase C (PLC)-beta3 is crucial for FcvarepsilonRI-mediated mast cell activation. Plcb3(-/-) mice showed blunted FcvarepsilonRI-dependent late-phase, but not acute, anaphylactic responses and airway inflammation. Accordingly, FcvarepsilonRI stimulation of Plcb3(-/-) mast cells exhibited reduced cytokine production but normal degranulation. Reduced cytokine production in Plcb3(-/-) cells could be accounted for by increased activity of the negative regulatory Src family kinase Lyn and reduced activities of the positive regulatory protein kinases MAPKs. Mechanistically, PLC-beta3 constitutively interacts with FcvarepsilonRI, Lyn, and SHP-1 (protein phosphatase). SHP-1 probably recognizes its substrates Lyn and MAPKs via the recently described kinase tyrosine-based inhibitory motif, KTIM. Consistent with PLC-beta3- and SHP-1-mediated repression of Lyn activity by dephosphorylation at Tyr396, FcvarepsilonRI-mediated phenotypes were similar in Plcb3(-/-) and SHP-1 mutant mast cells. Thus, we have defined a PLC-beta3- and SHP-1-mediated signaling pathway for FcvarepsilonRI-mediated cytokine production. |
