| First Author | Samayawardhena LA | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 10 | Pages | 5993-6002 |
| PubMed ID | 20944008 | Mgi Jnum | J:165625 |
| Mgi Id | MGI:4837942 | Doi | 10.4049/jimmunol.1001261 |
| Citation | Samayawardhena LA, et al. (2010) PTP{alpha} Activates Lyn and Fyn and Suppresses Hck to Negatively Regulate Fc{varepsilon}RI-Dependent Mast Cell Activation and Allergic Responses. J Immunol 185(10):5993-6002 |
| abstractText | Mast cell activation via FcepsilonRI involves activation of the Src family kinases (SFKs) Lyn, Fyn, and Hck that positively or, in the case of Lyn, negatively regulate cellular responses. Little is known of upstream activators of these SFKs in FcepsilonRI-dependent signaling. We investigated the role of receptor protein tyrosine phosphatase (PTP)alpha, a well-known activator of SFKs in diverse signaling systems, FcepsilonRI-mediated mast cell activation, and IgE-dependent allergic responses in mice. PTPalpha(-/-) bone marrow-derived mast cells hyperdegranulate and exhibit increased cytokine and cysteinyl leukotriene secretion, and PTPalpha(-/-) mice display enhanced IgE-dependent anaphylaxis. At or proximal to FcepsilonRI, PTPalpha(-/-) cells have reduced IgE-dependent activation of Lyn and Fyn, as well as reduced FcepsilonRI and SHIP phosphorylation. In contrast, Hck and Syk activation is enhanced. Syk hyperactivation correlated with its increased phosphorylation at positive regulatory sites and defective phosphorylation at a negative regulatory site. Distal to FcepsilonRI, we observed increased activation of PI3K and MAPK pathways. These findings demonstrate that PTPalpha activates the FcepsilonRI-coupled kinases Lyn and Fyn and suppresses Hck activity. Furthermore, the findings indicate that hyperactivation of PTPalpha(-/-) mast cells and enhanced IgE-dependent allergic responses of PTPalpha(-/-) mice are due to the ablated function of PTPalpha as a critical regulator of Lyn negative signaling. |
