| http://purl.uniprot.org/citations/17513616 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17513616 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17513616 | http://www.w3.org/2000/01/rdf-schema#comment | "IgE/antigen-dependent mast cell activation plays a central role in immediate hypersensitivity and other allergic reactions. The Src family tyrosine kinase (SFK) Lyn is activated by the cross-linking of high-affinity IgE receptors (FcepsilonRI). Activated Lyn phosphorylates the FcepsilonRI subunits, beta and gamma, leading to subsequent activation of various signaling pathways. Lyn also plays a negative regulatory function by activating negative regulatory molecules. Another SFK, Fyn, also contributes to mast cell degranulation by inducing Gab2-dependent microtubule formation. Here we show that a third SFK, Hck, plays a critical role in mast cell activation. Degranulation and cytokine production are reduced in FcepsilonRI-stimulated hck(-/-) mast cells. The reduced degranulation can be accounted for by defects in Gab2 phosphorylation and microtubule formation. Importantly, Lyn activity is elevated in hck(-/-) cells, leading to increased phosphorylation of several negative regulators. However, positive regulatory events, such as activation of Syk, Btk, JNK, p38, Akt, and NF-kappaB, are substantially reduced in hck(-/-) mast cells. Analysis of lyn(-/-)hck(-/-), lyn(-/-)FcepsilonRIbeta(-/-), and hck(-/-)FcepsilonRIbeta(-/-) cells shows that Hck exerts these functions via both Lyn-dependent and Lyn-independent mechanisms. Thus, this study has revealed a hierarchical regulation among SFK members to fine-tune mast cell activation."xsd:string |
| http://purl.uniprot.org/citations/17513616 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood-2007-01-066092"xsd:string |
| http://purl.uniprot.org/citations/17513616 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood-2007-01-066092"xsd:string |
| http://purl.uniprot.org/citations/17513616 | http://purl.uniprot.org/core/author | "Kawakami T."xsd:string |
| http://purl.uniprot.org/citations/17513616 | http://purl.uniprot.org/core/author | "Kawakami T."xsd:string |
| http://purl.uniprot.org/citations/17513616 | http://purl.uniprot.org/core/author | "Hong H."xsd:string |
| http://purl.uniprot.org/citations/17513616 | http://purl.uniprot.org/core/author | "Hong H."xsd:string |
| http://purl.uniprot.org/citations/17513616 | http://purl.uniprot.org/core/author | "Xiao W."xsd:string |
| http://purl.uniprot.org/citations/17513616 | http://purl.uniprot.org/core/author | "Xiao W."xsd:string |
| http://purl.uniprot.org/citations/17513616 | http://purl.uniprot.org/core/author | "Lowell C.A."xsd:string |
| http://purl.uniprot.org/citations/17513616 | http://purl.uniprot.org/core/author | "Lowell C.A."xsd:string |
| http://purl.uniprot.org/citations/17513616 | http://purl.uniprot.org/core/author | "Kawakami Y."xsd:string |
| http://purl.uniprot.org/citations/17513616 | http://purl.uniprot.org/core/author | "Kawakami Y."xsd:string |
| http://purl.uniprot.org/citations/17513616 | http://purl.uniprot.org/core/author | "Kitaura J."xsd:string |
| http://purl.uniprot.org/citations/17513616 | http://purl.uniprot.org/core/author | "Kitaura J."xsd:string |
| http://purl.uniprot.org/citations/17513616 | http://purl.uniprot.org/core/author | "Horejsi V."xsd:string |
| http://purl.uniprot.org/citations/17513616 | http://purl.uniprot.org/core/author | "Horejsi V."xsd:string |
| http://purl.uniprot.org/citations/17513616 | http://purl.uniprot.org/core/author | "Ra C."xsd:string |
| http://purl.uniprot.org/citations/17513616 | http://purl.uniprot.org/core/author | "Ra C."xsd:string |
| http://purl.uniprot.org/citations/17513616 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17513616 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17513616 | http://purl.uniprot.org/core/name | "Blood"xsd:string |
| http://purl.uniprot.org/citations/17513616 | http://purl.uniprot.org/core/name | "Blood"xsd:string |