Phospholipase C-ß3 regulates FcÉRI-mediated mast cell activation by recruiting the protein phosphatase SHP-1.
Immunity
; 34(6): 893-904, 2011 Jun 24.
Article
em En
| MEDLINE
| ID: mdl-21683628
ABSTRACT
Mast cells are major effectors in high-affinity IgE receptor (FcÉRI)-dependent allergic reactions. Here we show that phospholipase C (PLC)-ß3 is crucial for FcÉRI-mediated mast cell activation. Plcb3(-/-) mice showed blunted FcÉRI-dependent late-phase, but not acute, anaphylactic responses and airway inflammation. Accordingly, FcÉRI 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-ß3 constitutively interacts with FcÉRI, 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-ß3- and SHP-1-mediated repression of Lyn activity by dephosphorylation at Tyr396, FcÉRI-mediated phenotypes were similar in Plcb3(-/-) and SHP-1 mutant mast cells. Thus, we have defined a PLC-ß3- and SHP-1-mediated signaling pathway for FcÉRI-mediated cytokine production.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de IgE
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Proteína Tirosina Fosfatase não Receptora Tipo 6
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Fosfolipase C beta
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Mastócitos
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article