DYRK1A kinase positively regulates angiogenic responses in endothelial cells

Rozen, Esteban J.; Roewenstrunk, Julia Maria, 1981-; Barallobre, María José; Di Vona, Chiara, 1981-; Jung, Carole; Figueiredo, Ana F.; Luna, Jeroni; Fillat i Fonts, Cristina; Arbonés de Rafael, Maria Lourdes, 1959-; Graupera, Mariona; Valverde, M. A. (Miguel Ángel), 1963-; Luna Gargantilla, Susana de la

DYRK1A kinase positively regulates angiogenic responses in endothelial cells

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...

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Autores:	Rozen, Esteban J., Roewenstrunk, Julia Maria, 1981-, Barallobre, María José, Di Vona, Chiara, 1981-, Jung, Carole, Figueiredo, Ana F., Luna, Jeroni, Fillat i Fonts, Cristina, Arbonés de Rafael, Maria Lourdes, 1959-, Graupera, Mariona, Valverde, M. A. (Miguel Ángel), 1963-, Luna Gargantilla, Susana de la
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2018
País:	España
Institución:	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:	Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:	oai:recercat.cat:10230/35632
Acceso en línea:	http://hdl.handle.net/10230/35632 http://dx.doi.org/10.1016/j.celrep.2018.04.008
Access Level:	acceso abierto
Palabra clave:	Angiogenesis DYRK1A Endothelial cell NFAT VEGF VEGFR2

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spelling	DYRK1A kinase positively regulates angiogenic responses in endothelial cellsRozen, Esteban J.Roewenstrunk, Julia Maria, 1981-Barallobre, María JoséDi Vona, Chiara, 1981-Jung, CaroleFigueiredo, Ana F.Luna, JeroniFillat i Fonts, CristinaArbonés de Rafael, Maria Lourdes, 1959-Graupera, MarionaValverde, M. A. (Miguel Ángel), 1963-Luna Gargantilla, Susana de laAngiogenesisDYRK1AEndothelial cellNFATVEGFVEGFR2Angiogenesis 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.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.Elsevier201820182018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/35632http://dx.doi.org/10.1016/j.celrep.2018.04.008reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésCell Reports. 2018;23(6):1867-78info:eu-repo/grantAgreement/EC/FP7/317250info:eu-repo/grantAgreement/EC/H2020/675392info:eu-repo/grantAgreement/ES/1PE/BFU2013-44513info:eu-repo/grantAgreement/ES/1PE/BFU2016-76141-Pinfo:eu-repo/grantAgreement/ES/1PE/SAF2015-69762-R© 2018 The Author(s). Under a Creative Commons license http://creativecommons.org/licenses/by-nc-nd/4.0/http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/356322026-05-29T05:05:01Z
dc.title.none.fl_str_mv	DYRK1A kinase positively regulates angiogenic responses in endothelial cells
title	DYRK1A kinase positively regulates angiogenic responses in endothelial cells
spellingShingle	DYRK1A kinase positively regulates angiogenic responses in endothelial cells Rozen, Esteban J. Angiogenesis DYRK1A Endothelial cell NFAT VEGF VEGFR2
title_short	DYRK1A kinase positively regulates angiogenic responses in endothelial cells
title_full	DYRK1A kinase positively regulates angiogenic responses in endothelial cells
title_fullStr	DYRK1A kinase positively regulates angiogenic responses in endothelial cells
title_full_unstemmed	DYRK1A kinase positively regulates angiogenic responses in endothelial cells
title_sort	DYRK1A kinase positively regulates angiogenic responses in endothelial cells
dc.creator.none.fl_str_mv	Rozen, Esteban J. Roewenstrunk, Julia Maria, 1981- Barallobre, María José Di Vona, Chiara, 1981- Jung, Carole Figueiredo, Ana F. Luna, Jeroni Fillat i Fonts, Cristina Arbonés de Rafael, Maria Lourdes, 1959- Graupera, Mariona Valverde, M. A. (Miguel Ángel), 1963- Luna Gargantilla, Susana de la
author	Rozen, Esteban J.
author_facet	Rozen, Esteban J. Roewenstrunk, Julia Maria, 1981- Barallobre, María José Di Vona, Chiara, 1981- Jung, Carole Figueiredo, Ana F. Luna, Jeroni Fillat i Fonts, Cristina Arbonés de Rafael, Maria Lourdes, 1959- Graupera, Mariona Valverde, M. A. (Miguel Ángel), 1963- Luna Gargantilla, Susana de la
author_role	author
author2	Roewenstrunk, Julia Maria, 1981- Barallobre, María José Di Vona, Chiara, 1981- Jung, Carole Figueiredo, Ana F. Luna, Jeroni Fillat i Fonts, Cristina Arbonés de Rafael, Maria Lourdes, 1959- Graupera, Mariona Valverde, M. A. (Miguel Ángel), 1963- Luna Gargantilla, Susana de la
author2_role	author author author author author author author author author author author
dc.subject.none.fl_str_mv	Angiogenesis DYRK1A Endothelial cell NFAT VEGF VEGFR2
topic	Angiogenesis DYRK1A Endothelial cell NFAT VEGF VEGFR2
description	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.
publishDate	2018
dc.date.none.fl_str_mv	2018 2018 2018
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	http://hdl.handle.net/10230/35632 http://dx.doi.org/10.1016/j.celrep.2018.04.008
url	http://hdl.handle.net/10230/35632 http://dx.doi.org/10.1016/j.celrep.2018.04.008
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Cell Reports. 2018;23(6):1867-78 info:eu-repo/grantAgreement/EC/FP7/317250 info:eu-repo/grantAgreement/EC/H2020/675392 info:eu-repo/grantAgreement/ES/1PE/BFU2013-44513 info:eu-repo/grantAgreement/ES/1PE/BFU2016-76141-P info:eu-repo/grantAgreement/ES/1PE/SAF2015-69762-R
dc.rights.none.fl_str_mv	http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf application/pdf
dc.publisher.none.fl_str_mv	Elsevier
publisher.none.fl_str_mv	Elsevier
dc.source.none.fl_str_mv	reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str	Recercat. Dipósit de la Recerca de Catalunya
collection	Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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DYRK1A kinase positively regulates angiogenic responses in endothelial cells

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