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DYRK1A kinase positively regulates angiogenic responses in endothelial cells

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dc.contributor.author Rozen, Esteban J.
dc.contributor.author Roewenstrunk, Julia Maria, 1981-
dc.contributor.author Barallobre, María José
dc.contributor.author Di Vona, Chiara, 1981-
dc.contributor.author Jung, Carole
dc.contributor.author Figueiredo, Ana F.
dc.contributor.author Luna, Jeroni
dc.contributor.author Fillat i Fonts, Cristina
dc.contributor.author Arbonés de Rafael, Maria Lourdes, 1959-
dc.contributor.author Graupera, Mariona
dc.contributor.author Valverde, M. A. (Miguel Ángel), 1963-
dc.contributor.author Luna Gargantilla, Susana de la
dc.date.accessioned 2018-10-23T07:46:05Z
dc.date.available 2018-10-23T07:46:05Z
dc.date.issued 2018
dc.identifier.citation Rozen EJ, Roewenstrunk J, Barallobre MJ, Di Vona C, Jung C, Figueiredo AF et al. DYRK1A kinase positively regulates angiogenic responses in endothelial cells. Cell Rep. 2018;23(6):1867-78. DOI: 10.1016/j.celrep.2018.04.008
dc.identifier.issn 2211-1247
dc.identifier.uri http://hdl.handle.net/10230/35632
dc.description.abstract Angiogenesis is a highly regulated process essential for organ development and maintenance, and its deregulation contributes to inflammation, cardiac disorders, and cancer. The Ca2+/nuclear factor of activated T cells (NFAT) signaling pathway is central to endothelial cell angiogenic responses, and it is activated by stimuli like vascular endothelial growth factor (VEGF) A. NFAT phosphorylation by dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs) is thought to be an inactivating event. Contrary to expectations, we show that the DYRK family member DYRK1A positively regulates VEGF-dependent NFAT transcriptional responses in primary endothelial cells. DYRK1A silencing reduces intracellular Ca2+ influx in response to VEGF, which dampens NFAT activation. The effect is exerted at the level of VEGFR2 accumulation leading to impairment in PLCγ1 activation. Notably, Dyrk1a heterozygous mice show defects in developmental retinal vascularization. Our data establish a regulatory circuit, DYRK1A/ Ca2+/NFAT, to fine-tune endothelial cell proliferation and angiogenesis.
dc.description.sponsorship This work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO grants BFU2013-44513 and BFU2016-76141-P to S.L., SAF2015-69762R to M.A.V., SAF2014-59950-P to M.G., BIO2014-57716-C2-R to C.F., and SAF2016-77971-R to M.L.A.), “La Marató de TV3” to S.L., the Instituto de Salud Carlos III (IIS10/00014 to C.F. and RD12/0042/0014 to M.A.V.), FEDER Funds to M.A.V., the Secretariat of Universities and Research-Generalitat de Catalunya (2014SGR674), the European CommissionFP7/2007-2013, and 2020 Research and Innovation Programmes (grant agreement 317250 and Marie Skłodowska-Curie grant agreement 675392). E.J.R., J.L., and M.J.B. are supported by CIBERER, J.R. is an FPI predoctoral fellow (BES-2011-045867), C.J. is a Juan de la Cierva postdoctoral researcher (JCI-2011-11140), and A.F.F. is a Marie Skłodowska-Curie ESR fellow.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Cell Reports. 2018;23(6):1867-78
dc.rights © 2018 The Author(s). Under a Creative Commons license http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.title DYRK1A kinase positively regulates angiogenic responses in endothelial cells
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2018.04.008
dc.subject.keyword Angiogenesis
dc.subject.keyword DYRK1A
dc.subject.keyword Endothelial cell
dc.subject.keyword NFAT
dc.subject.keyword VEGF
dc.subject.keyword VEGFR2
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/317250
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/675392
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2013-44513
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2016-76141-P
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-69762-R
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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