| First Author | Hazenbos WL | Year | 2011 |
| Journal | Blood | Volume | 118 |
| Issue | 16 | Pages | 4377-83 |
| PubMed ID | 21865342 | Mgi Jnum | J:178391 |
| Mgi Id | MGI:5298290 | Doi | 10.1182/blood-2011-02-338053 |
| Citation | Hazenbos WL, et al. (2011) Impaired FcepsilonRI stability, signaling, and effector functions in murine mast cells lacking glycosylphosphatidylinositol-anchored proteins. Blood 118(16):4377-83 |
| abstractText | A key event and potential therapeutic target in allergic and asthmatic diseases is signaling by the IgE receptor FcepsilonRI, which depends on its interactions with Src family kinases (SFK). Here we tested the hypothesis that glycosylphosphatidylinositiol-anchored proteins (GPI-AP) are involved in FcepsilonRI signaling, based on previous observations that GPI-AP colocalize with and mediate activation of SFK. We generated mice with a hematopoietic cell-specific GPI-AP deficiency by targeted disruption of the GPI biosynthesis gene PigA. In these mice, IgE-mediated passive cutaneous anaphylaxis was largely abolished. PigA-deficient mast cells cultured from these mice showed impaired degranulation in response to stimulation with IgE and antigen in vitro, despite normal IgE binding and antigen-induced FcepsilonRI aggregation. On stimulation of these cells with IgE and antigen, coprecipitation of the FcepsilonRI alpha-chain with the gamma-chain and beta-chain was markedly reduced. As a result, IgE/antigen-induced FcepsilonRI-Lyn association and gamma-chain tyrosine phosphorylation were both impaired in PigA-deficient cells. These data provide genetic evidence for an unanticipated key role of GPI-AP in FcepsilonRI interchain interactions and early FcepsilonRI signaling events, necessary for antigen-induced mast cell degranulation. |
