Coordinated activation of the Rac-GAP β2-chimaerin by an atypical proline-rich domain and diacylglycerol

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dc.contributor.authorGutiérrez Uzquiza, Álvaro
dc.contributor.authorColon-Gonzalez, Francheska
dc.contributor.authorLeonard, Thomas A.
dc.contributor.authorCanagarajah, Bertram J.
dc.contributor.authorWang, HongBin
dc.contributor.authorMayer, Bruce J.
dc.contributor.authorHurley, James H.
dc.contributor.authorKazanietz, Marcelo G.
dc.date.accessioned2024-01-17T09:01:30Z
dc.date.available2024-01-17T09:01:30Z
dc.date.issued2013-05-14
dc.description.abstractChimaerins, a family of GTPase activating proteins for the small G-protein Rac, have been implicated in development, neuritogenesis and cancer. These Rac-GTPase activating proteins are regulated by the lipid second messenger diacylglycerol generated by tyrosine kinases such as the epidermal growth factor receptor. Here we identify an atypical proline-rich motif in chimaerins that binds to the adaptor protein Nck1. Unlike most Nck1 partners, chimaerins bind to the third SH3 domain of Nck1. This association is mediated by electrostatic interactions of basic residues within the Pro-rich motif with acidic clusters in the SH3 domain. Epidermal growth factor promotes the binding of β2-chimaerin to Nck1 in the cell periphery in a diacylglycerol-dependent manner. Moreover, β2-chimaerin translocation to the plasma membrane and its peripheral association with Rac1 requires Nck1. Our studies underscore a coordinated mechanism for β2-chimaerin activation that involves lipid interactions via the C1 domain and protein-protein interactions via the N-terminal proline-rich region.
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Farmacia
dc.description.refereedTRUE
dc.description.sponsorshipNational Institutes of Health
dc.description.sponsorshipOrganización Europea de Biología Molecular
dc.description.statuspub
dc.identifier.citationGutierrez-Uzquiza A, Colon-Gonzalez F, Leonard TA, Canagarajah BJ, Wang H, Mayer BJ, et al. Coordinated activation of the Rac-GAP β2-chimaerin by an atypical proline-rich domain and diacylglycerol. Nat Commun 2013;4:1849. https://doi.org/10.1038/ncomms28
dc.identifier.doi10.1038/ncomms2834
dc.identifier.issn2041-1723
dc.identifier.officialurlhttps://doi.org/10.1038/ncomms2834
dc.identifier.urihttps://hdl.handle.net/20.500.14352/93524
dc.journal.titleNature Communications
dc.language.isoeng
dc.page.initial1849
dc.page.total13
dc.relation.projectIDinfo:eu-repo/grantAgreement/CA74197
dc.relation.projectIDinfo:eu-repo/grantAgreement/CA139120
dc.relation.projectIDinfo:eu-repo/grantAgreement/CA82258
dc.rights.accessRightsrestricted access
dc.subject.cdu612.015
dc.subject.ucmBiología molecular (Química)
dc.subject.unesco2302 Bioquímica
dc.titleCoordinated activation of the Rac-GAP β2-chimaerin by an atypical proline-rich domain and diacylglycerol
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number4
dspace.entity.typePublication
relation.isAuthorOfPublicationfe7d7e09-f48f-4104-b627-5f056790b029
relation.isAuthorOfPublication.latestForDiscoveryfe7d7e09-f48f-4104-b627-5f056790b029
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