| pubmed-article:16511561 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:16511561 | lifeskim:mentions | umls-concept:C0031715 | lld:lifeskim |
| pubmed-article:16511561 | lifeskim:mentions | umls-concept:C0037083 | lld:lifeskim |
| pubmed-article:16511561 | lifeskim:mentions | umls-concept:C0025543 | lld:lifeskim |
| pubmed-article:16511561 | lifeskim:mentions | umls-concept:C1710082 | lld:lifeskim |
| pubmed-article:16511561 | lifeskim:mentions | umls-concept:C1709694 | lld:lifeskim |
| pubmed-article:16511561 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:16511561 | pubmed:issue | 6 | lld:pubmed |
| pubmed-article:16511561 | pubmed:dateCreated | 2006-3-22 | lld:pubmed |
| pubmed-article:16511561 | pubmed:abstractText | Bidirectional signaling triggered by interacting ephrinB receptors (EphB) and ephrinB ligands is crucial for development and function of the vascular and nervous systems. A signaling cascade triggered by this interaction involves activation of Src kinase and phosphorylation of ephrinB. The mechanism, however, by which EphB activates Src in the ephrinB-expressing cells is unknown. Here we show that EphB stimulates a metalloproteinase cleavage of ephrinB2, producing a carboxy-terminal fragment that is further processed by PS1/gamma-secretase to produce intracellular peptide ephrinB2/CTF2. This peptide binds Src and inhibits its association with inhibitory kinase Csk, allowing autophosphorylation of Src at residue tyr418. EphrinB2/CTF2-activated Src phosphorylates ephrinB2 and inhibits its processing by gamma-secretase. These data show that the PS1/gamma-secretase system controls Src activation and ephrinB phosphorylation by regulating production of Src activator ephrinB2/CTF2. Accordingly, gamma-secretase inhibitors prevented the EphB-induced sprouting of endothelial cells and the recruitment of Grb4 to ephrinB. PS1 FAD and gamma-secretase dominant-negative mutants inhibited the EphB-induced cleavage of ephrinB2 and Src autophosphorylation, raising the possibility that FAD mutants interfere with the functions of Src and ephrinB2 in the CNS. | lld:pubmed |
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| pubmed-article:16511561 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16511561 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16511561 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:16511561 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:16511561 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16511561 | pubmed:month | Mar | lld:pubmed |
| pubmed-article:16511561 | pubmed:issn | 0261-4189 | lld:pubmed |
| pubmed-article:16511561 | pubmed:author | pubmed-author:RobakisNikola... | lld:pubmed |
| pubmed-article:16511561 | pubmed:author | pubmed-author:SerbanGeoG | lld:pubmed |
| pubmed-article:16511561 | pubmed:author | pubmed-author:Georgakopoulo... | lld:pubmed |
| pubmed-article:16511561 | pubmed:author | pubmed-author:BakiLiaL | lld:pubmed |
| pubmed-article:16511561 | pubmed:author | pubmed-author:GhersiEnricoE | lld:pubmed |
| pubmed-article:16511561 | pubmed:author | pubmed-author:LitterstClaud... | lld:pubmed |
| pubmed-article:16511561 | pubmed:author | pubmed-author:XuChiJieC | lld:pubmed |
| pubmed-article:16511561 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:16511561 | pubmed:day | 22 | lld:pubmed |
| pubmed-article:16511561 | pubmed:volume | 25 | lld:pubmed |
| pubmed-article:16511561 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:16511561 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:16511561 | pubmed:pagination | 1242-52 | lld:pubmed |
| pubmed-article:16511561 | pubmed:dateRevised | 2011-11-2 | lld:pubmed |
