000046280 001__ 46280
000046280 005__ 20200423204152.0
000046280 0247_ $$2pmid$$apmid:15554700
000046280 0247_ $$2DOI$$a10.1021/bi0485068
000046280 0247_ $$2WOS$$aWOS:000225353300007
000046280 0247_ $$2Handle$$a2128/707
000046280 037__ $$aPreJuSER-46280
000046280 041__ $$aeng
000046280 082__ $$a570
000046280 084__ $$2WoS$$aBiochemistry & Molecular Biology
000046280 1001_ $$0P:(DE-HGF)0$$aBauer, F.$$b0
000046280 245__ $$aCharacterization of Lck-binding elements in the herpesviral regulatory Tip protein
000046280 260__ $$aColumbus, Ohio$$bAmerican Chemical Society$$c2004
000046280 300__ $$a14932-9
000046280 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article
000046280 3367_ $$2DataCite$$aOutput Types/Journal article
000046280 3367_ $$00$$2EndNote$$aJournal Article
000046280 3367_ $$2BibTeX$$aARTICLE
000046280 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000046280 3367_ $$2DRIVER$$aarticle
000046280 440_0 $$0798$$aBiochemistry$$v43$$x0006-2960$$y47
000046280 500__ $$aRecord converted from VDB: 12.11.2012
000046280 520__ $$aHerpesvirus saimiri encodes a tyrosine kinase interacting protein (Tip) that binds to T-cell-specific tyrosine kinase Lck via multiple sequence motifs and controls its activity. The regulation of Lck by Tip represents a key mechanism in the transformation of human T-lymphocytes during herpesviral infection. In this study, the interaction of Tip with the regulatory SH3 and SH2 domains of Lck was investigated by biophysical and computational techniques. NMR spectroscopy of isotopically labeled Tip(140-191) revealed that the interaction with the LckSH3 domain is not restricted to the classical proline-rich motif, but also involves the C-terminally adjacent residues which pack into a hydrophobic pocket on the surface of the SH3 domain, thus playing a likely role in mediating binding specificity. Fluorescence binding studies of Tip further demonstrate that Tyr127 in its phosphorylated form represents a strong ligand of the LckSH2 domain, indicating the presence of an additional Lck interaction motif. In contrast, Tyr114, known to be essential for STAT-3 binding, does not interact with the LckSH2 domain, showing that the tyrosines in Tip exhibit distinct binding specificity. The existence of numerous interaction sites between Tip and the regulatory domains of Lck implies a complex regulatory mechanism and may have evolved to allow a gradual regulation of Lck activity in different pathogenic states.
000046280 536__ $$0G:(DE-Juel1)FUEK255$$2G:(DE-HGF)$$aNeurowissenschaften$$cL01$$x0
000046280 588__ $$aDataset connected to Web of Science, Pubmed
000046280 650_2 $$2MeSH$$aAmino Acid Sequence
000046280 650_2 $$2MeSH$$aCircular Dichroism
000046280 650_2 $$2MeSH$$aCloning, Molecular
000046280 650_2 $$2MeSH$$aConserved Sequence
000046280 650_2 $$2MeSH$$aHerpesvirus 2, Saimiriine: chemistry
000046280 650_2 $$2MeSH$$aHerpesvirus 2, Saimiriine: enzymology
000046280 650_2 $$2MeSH$$aHerpesvirus 2, Saimiriine: metabolism
000046280 650_2 $$2MeSH$$aHydrophobic and Hydrophilic Interactions
000046280 650_2 $$2MeSH$$aKinetics
000046280 650_2 $$2MeSH$$aLigands
000046280 650_2 $$2MeSH$$aLymphocyte Specific Protein Tyrosine Kinase p56(lck): chemistry
000046280 650_2 $$2MeSH$$aLymphocyte Specific Protein Tyrosine Kinase p56(lck): metabolism
000046280 650_2 $$2MeSH$$aModels, Molecular
000046280 650_2 $$2MeSH$$aMolecular Sequence Data
000046280 650_2 $$2MeSH$$aNuclear Magnetic Resonance, Biomolecular
000046280 650_2 $$2MeSH$$aPhosphoproteins: chemistry
000046280 650_2 $$2MeSH$$aPhosphoproteins: genetics
000046280 650_2 $$2MeSH$$aPhosphoproteins: isolation & purification
000046280 650_2 $$2MeSH$$aPhosphoproteins: metabolism
000046280 650_2 $$2MeSH$$aPhosphotyrosine: chemistry
000046280 650_2 $$2MeSH$$aProtein Binding
000046280 650_2 $$2MeSH$$aProtein Structure, Secondary
000046280 650_2 $$2MeSH$$aProtons
000046280 650_2 $$2MeSH$$aSequence Homology, Amino Acid
000046280 650_2 $$2MeSH$$aSpectrometry, Fluorescence
000046280 650_2 $$2MeSH$$aViral Proteins: chemistry
000046280 650_2 $$2MeSH$$aViral Proteins: genetics
000046280 650_2 $$2MeSH$$aViral Proteins: isolation & purification
000046280 650_2 $$2MeSH$$aViral Proteins: metabolism
000046280 650_7 $$00$$2NLM Chemicals$$aLigands
000046280 650_7 $$00$$2NLM Chemicals$$aPhosphoproteins
000046280 650_7 $$00$$2NLM Chemicals$$aProtons
000046280 650_7 $$00$$2NLM Chemicals$$aViral Proteins
000046280 650_7 $$00$$2NLM Chemicals$$atyrosine kinase interacting protein, Saimiriine herpesvirus 2
000046280 650_7 $$021820-51-9$$2NLM Chemicals$$aPhosphotyrosine
000046280 650_7 $$0EC 2.7.10.2$$2NLM Chemicals$$aLymphocyte Specific Protein Tyrosine Kinase p56(lck)
000046280 650_7 $$2WoSType$$aJ
000046280 7001_ $$0P:(DE-HGF)0$$aHofinger, E.$$b1
000046280 7001_ $$0P:(DE-Juel1)VDB630$$aHoffmann, S.$$b2$$uFZJ
000046280 7001_ $$0P:(DE-HGF)0$$aRösch, P.$$b3
000046280 7001_ $$0P:(DE-HGF)0$$aSchweimer, K.$$b4
000046280 7001_ $$0P:(DE-HGF)0$$aSticht, H.$$b5
000046280 773__ $$0PERI:(DE-600)1472258-6$$a10.1021/bi0485068$$gVol. 43, p. 14932-9$$p14932-9$$q43<14932-9$$tBiochemistry$$v43$$x0006-2960$$y2004
000046280 8567_ $$uhttp://hdl.handle.net/2128/707$$uhttp://dx.doi.org/10.1021/bi0485068
000046280 8564_ $$uhttps://juser.fz-juelich.de/record/46280/files/72895.pdf$$yOpenAccess
000046280 8564_ $$uhttps://juser.fz-juelich.de/record/46280/files/72895.jpg?subformat=icon-1440$$xicon-1440$$yOpenAccess
000046280 8564_ $$uhttps://juser.fz-juelich.de/record/46280/files/72895.jpg?subformat=icon-180$$xicon-180$$yOpenAccess
000046280 8564_ $$uhttps://juser.fz-juelich.de/record/46280/files/72895.jpg?subformat=icon-640$$xicon-640$$yOpenAccess
000046280 909CO $$ooai:juser.fz-juelich.de:46280$$pdnbdelivery$$pVDB$$pdriver$$popen_access$$popenaire
000046280 9131_ $$0G:(DE-Juel1)FUEK255$$bLeben$$kL01$$lFunktion und Dysfunktion des Nervensystems$$vNeurowissenschaften$$x0
000046280 9141_ $$aNachtrag$$y2004
000046280 915__ $$0StatID:(DE-HGF)0010$$aJCR/ISI refereed
000046280 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000046280 9201_ $$0I:(DE-Juel1)VDB58$$d31.12.2006$$gIBI$$kIBI-2$$lBiologische Strukturforschung$$x0
000046280 970__ $$aVDB:(DE-Juel1)72895
000046280 9801_ $$aFullTexts
000046280 980__ $$aVDB
000046280 980__ $$aJUWEL
000046280 980__ $$aConvertedRecord
000046280 980__ $$ajournal
000046280 980__ $$aI:(DE-Juel1)ISB-2-20090406
000046280 980__ $$aUNRESTRICTED
000046280 980__ $$aI:(DE-Juel1)ICS-6-20110106
000046280 980__ $$aFullTexts
000046280 981__ $$aI:(DE-Juel1)IBI-7-20200312
000046280 981__ $$aI:(DE-Juel1)ISB-2-20090406
000046280 981__ $$aI:(DE-Juel1)ICS-6-20110106