Pérez, YolandaMattei, MarianoIgea, AnaAmata, IreneGairí Tahull, MargaridaNebreda, Àngel R.Bernadó Peretó, PauPons Vallès, Miquel2013-07-122013-07-122013-02-182045-2322https://hdl.handle.net/2445/44749c-Src is a non-receptor tyrosine kinase involved in numerous signal transduction pathways. The kinase,SH3 and SH2 domains of c-Src are attached to the membrane-anchoring SH4 domain through the flexible Unique domain. Here we show intra- and intermolecular interactions involving the Unique and SH3 domains suggesting the presence of a previously unrecognized additional regulation layer in c-Src. We have characterized lipid binding by the Unique and SH3 domains, their intramolecular interaction and its allosteric modulation by a SH3-binding peptide or by Calcium-loaded calmodulin binding to the Unique domain. We also show reduced lipid binding following phosphorylation at conserved sites of the Unique domain. Finally, we show that injection of full-length c-Src with mutations that abolish lipid binding by the Unique domain causes a strong in vivo phenotype distinct from that of wild-type c-Src in a Xenopus oocyte model system, confirming the functional role of the Unique domain in c-Src regulation.9 p.application/pdfengcc-by-nc-nd (c) Pérez, Yolanda et al., 2013http://creativecommons.org/licenses/by-nc-nd/3.0/esProteïnes quinasesLípidsReceptors cel·lularsRegulació cel·lularLligands (Bioquímica)Protein kinasesLipidsCell receptorsCellular control mechanismsLigands (Biochemistry)info:eu-repo/semantics/article6228752013-07-12info:eu-repo/semantics/openAccess