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dc.contributor.author
Creixell, Pau  
dc.contributor.author
Palmeri, Antonio  
dc.contributor.author
Miller, Chad J.  
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Lou, Hua Jane  
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Santini, Cristina C.  
dc.contributor.author
Nielsen, Morten  
dc.contributor.author
Turk, Benjamin E.  
dc.contributor.author
Linding, Rune  
dc.date.available
2018-06-19T18:42:54Z  
dc.date.issued
2015-09  
dc.identifier.citation
Creixell, Pau; Palmeri, Antonio; Miller, Chad J.; Lou, Hua Jane; Santini, Cristina C.; et al.; Unmasking Determinants of Specificity in the Human Kinome; Cell Press; Cell; 163; 1; 9-2015; 187-201  
dc.identifier.issn
0092-8674  
dc.identifier.uri
http://hdl.handle.net/11336/49381  
dc.description.abstract
Protein kinases control cellular responses to environmental cues by swift and accurate signal processing. Breakdowns in this high-fidelity capability are a driving force in cancer and other diseases. Thus, our limited understanding of which amino acids in the kinase domain encode substrate specificity, the so-called determinants of specificity (DoS), constitutes a major obstacle in cancer signaling. Here, we systematically discover several DoS and experimentally validate three of them, named the αC1, αC3, and APE-7 residues. We demonstrate that DoS form sparse networks of non-conserved residues spanning distant regions. Our results reveal a likely role for inter-residue allostery in specificity and an evolutionary decoupling of kinase activity and specificity, which appear loaded on independent groups of residues. Finally, we uncover similar properties driving SH2 domain specificity and demonstrate how the identification of DoS can be utilized to elucidate a greater understanding of the role of signaling networks in cancer (Creixell et al., 2015 [this issue of Cell]).  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Cell Press  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
Protein Kinases  
dc.subject
Determinants of Specificity  
dc.subject.classification
Salud Pública y Medioambiental  
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Ciencias de la Salud  
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CIENCIAS MÉDICAS Y DE LA SALUD  
dc.title
Unmasking Determinants of Specificity in the Human Kinome  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2018-06-19T16:51:38Z  
dc.journal.volume
163  
dc.journal.number
1  
dc.journal.pagination
187-201  
dc.journal.pais
Estados Unidos  
dc.description.fil
Fil: Creixell, Pau. Technical University of Denmark; Dinamarca  
dc.description.fil
Fil: Palmeri, Antonio. Universita Tor Vergata; Italia  
dc.description.fil
Fil: Miller, Chad J.. University of Yale; Estados Unidos  
dc.description.fil
Fil: Lou, Hua Jane. University of Yale; Estados Unidos  
dc.description.fil
Fil: Santini, Cristina C.. Universidad de Copenhagen; Dinamarca. Technical University of Denmark; Dinamarca  
dc.description.fil
Fil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina  
dc.description.fil
Fil: Turk, Benjamin E.. University of Yale; Estados Unidos  
dc.description.fil
Fil: Linding, Rune. Technical University of Denmark; Dinamarca. Universidad de Copenhagen; Dinamarca  
dc.journal.title
Cell  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.cell.2015.08.057  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0092867415011095