| http://purl.uniprot.org/citations/16977320 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16977320 | http://www.w3.org/2000/01/rdf-schema#comment | "Eph receptor tyrosine kinases (RTKs) mediate numerous developmental processes. Their activity is regulated by auto-phosphorylation on two tyrosines within the juxtamembrane segment (JMS) immediately N-terminal to the kinase domain (KD). Here, we probe the molecular details of Eph kinase activation through mutational analysis, X-ray crystallography and NMR spectroscopy on auto-inhibited and active EphB2 and EphA4 fragments. We show that a Tyr750Ala gain-of-function mutation in the KD and JMS phosphorylation independently induce disorder of the JMS and its dissociation from the KD. Our X-ray analyses demonstrate that this occurs without major conformational changes to the KD and with only partial ordering of the KD activation segment. However, conformational exchange for helix alphaC in the N-terminal KD lobe and for the activation segment, coupled with increased inter-lobe dynamics, is observed upon kinase activation in our NMR analyses. Overall, our results suggest that a change in inter-lobe dynamics and the sampling of catalytically competent conformations for helix alphaC and the activation segment rather than a transition to a static active conformation underlies Eph RTK activation."xsd:string |
| http://purl.uniprot.org/citations/16977320 | http://purl.org/dc/terms/identifier | "doi:10.1038/sj.emboj.7601315"xsd:string |
| http://purl.uniprot.org/citations/16977320 | http://purl.uniprot.org/core/author | "Lin H."xsd:string |
| http://purl.uniprot.org/citations/16977320 | http://purl.uniprot.org/core/author | "Pawson T."xsd:string |
| http://purl.uniprot.org/citations/16977320 | http://purl.uniprot.org/core/author | "Sicheri F."xsd:string |
| http://purl.uniprot.org/citations/16977320 | http://purl.uniprot.org/core/author | "Forman-Kay J.D."xsd:string |
| http://purl.uniprot.org/citations/16977320 | http://purl.uniprot.org/core/author | "Wybenga-Groot L.E."xsd:string |
| http://purl.uniprot.org/citations/16977320 | http://purl.uniprot.org/core/author | "Warner N."xsd:string |
| http://purl.uniprot.org/citations/16977320 | http://purl.uniprot.org/core/author | "Wiesner S."xsd:string |
| http://purl.uniprot.org/citations/16977320 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/16977320 | http://purl.uniprot.org/core/name | "EMBO J"xsd:string |
| http://purl.uniprot.org/citations/16977320 | http://purl.uniprot.org/core/pages | "4686-4696"xsd:string |
| http://purl.uniprot.org/citations/16977320 | http://purl.uniprot.org/core/title | "A change in conformational dynamics underlies the activation of Eph receptor tyrosine kinases."xsd:string |
| http://purl.uniprot.org/citations/16977320 | http://purl.uniprot.org/core/volume | "25"xsd:string |
| http://purl.uniprot.org/citations/16977320 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/16977320 |
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