| http://purl.uniprot.org/citations/16873377 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16873377 | http://www.w3.org/2000/01/rdf-schema#comment | "The scaffolding adapter Gab2 mediates cell signaling and responses evoked by various extracellular stimuli including several growth factors. Kit, the receptor for stem cell factor (SCF), plays a critical role in the proliferation and differentiation of a variety of cell types, including mast cells. Kit, via Tyr(567) and Tyr(719), activates Src family kinases (SFK) and PI3K respectively, which converge on the activation of a Rac/JNK pathway required for mast cell proliferation. However, how Kit Tyr(567) signals to Rac/JNK is not well understood. By analyzing Gab2(-/-) mast cells, we find that Gab2 is required for SCF-evoked proliferation, activation of Rac/JNK, and Ras. Upon Kit activation in wild-type mast cells, Gab2 becomes tyrosyl-phosphorylated and associates with Kit and Shp-2. Tyr(567), an SFK binding site in Kit, and SFK activity were required for Gab2 tyrosyl phosphorylation and association with Shp-2. By re-expressing Gab2 or a Gab2 mutant that cannot bind Shp-2 in Gab2(-/-) mast cells or acutely by deleting Shp-2 in mast cells, we found that Gab2 requires Shp-2 for SCF-evoked Rac/JNK, Ras activation, and mast cell proliferation. Lastly, by analyzing mast cells from mice with compound Gab2 and Kit Y719F mutations (i.e., Gab2(-/-): KitY719F/Y719F mice), we find that Gab2, acting in a parallel pathway to PI3K from Kit Tyr(719), regulates mast cell proliferation and development in specific tissues. Our data show that Gab2 via Shp-2 is critical for transmitting signals from Kit Tyr(567) to activate the Rac/JNK pathway controlling mast cell proliferation, which likely contributes to mast cell development in specific tissues."xsd:string |
| http://purl.uniprot.org/citations/16873377 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m603742200"xsd:string |
| http://purl.uniprot.org/citations/16873377 | http://purl.uniprot.org/core/author | "Luo J."xsd:string |
| http://purl.uniprot.org/citations/16873377 | http://purl.uniprot.org/core/author | "Gu H."xsd:string |
| http://purl.uniprot.org/citations/16873377 | http://purl.uniprot.org/core/author | "Besmer P."xsd:string |
| http://purl.uniprot.org/citations/16873377 | http://purl.uniprot.org/core/author | "Wang Y."xsd:string |
| http://purl.uniprot.org/citations/16873377 | http://purl.uniprot.org/core/author | "Yang W."xsd:string |
| http://purl.uniprot.org/citations/16873377 | http://purl.uniprot.org/core/author | "Yu M."xsd:string |
| http://purl.uniprot.org/citations/16873377 | http://purl.uniprot.org/core/author | "Kanakura Y."xsd:string |
| http://purl.uniprot.org/citations/16873377 | http://purl.uniprot.org/core/author | "Mizuki M."xsd:string |
| http://purl.uniprot.org/citations/16873377 | http://purl.uniprot.org/core/author | "Neel B.G."xsd:string |
| http://purl.uniprot.org/citations/16873377 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/16873377 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/16873377 | http://purl.uniprot.org/core/pages | "28615-28626"xsd:string |
| http://purl.uniprot.org/citations/16873377 | http://purl.uniprot.org/core/title | "The scaffolding adapter Gab2, via Shp-2, regulates kit-evoked mast cell proliferation by activating the Rac/JNK pathway."xsd:string |
| http://purl.uniprot.org/citations/16873377 | http://purl.uniprot.org/core/volume | "281"xsd:string |
| http://purl.uniprot.org/citations/16873377 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/16873377 |
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| http://purl.uniprot.org/uniprot/#_C7ENW2-mappedCitation-16873377 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16873377 |