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, Barallobre, María José, Di Vona, Chiara, Jung, Carole, Figueiredo, Ana F., Luna Cornadó, Jeroni, Fillat i Fonts, Cristina, Arbonés de Rafael, Maria Lourdes, 1959-, Graupera i Garcia-Milà, Mariona, Valverde, Miguel Ángel, Luna, Susana de la
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/172465
Acceso en línea:https://hdl.handle.net/2445/172465
Access Level:acceso abierto
Palabra clave:Angiogènesi
Càncer
Neovascularization
Cancer
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spelling DYRK1A Kinase Positively Regulates Angiogenic Responses in Endothelial CellsRozen, Esteban J.Roewenstrunk, JuliaBarallobre, María JoséDi Vona, ChiaraJung, CaroleFigueiredo, Ana F.Luna Cornadó, JeroniFillat i Fonts, CristinaArbonés de Rafael, Maria Lourdes, 1959-Graupera i Garcia-Milà, MarionaValverde, Miguel ÁngelLuna, Susana de laAngiogènesiCàncerNeovascularizationCancerAngiogenesis 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 PLC gamma 1 activation. Notably, Dyrk1 alpha heterozygous mice show defects in developmental retinal vascularization. Our data establish a regulatory circuit, DYRK1A/C-a2+/NFAT, to fine-tune endothelial cell proliferation and angiogenesis.Cell Press2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/172465Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1016/j.celrep.2018.04.008Cell Reports, 2018, vol. 23, num. 6, Pp 1867-1878https://doi.org/10.1016/j.celrep.2018.04.008info:eu-repo/grantAgreement/EC/H2020/675392info:eu-repo/grantAgreement/EC/FP7/317250cc-by-nc-nd (c) Rozen et al., 2018http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1724652026-05-27T06:46:51Z
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.
Angiogènesi
Càncer
Neovascularization
Cancer
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
Barallobre, María José
Di Vona, Chiara
Jung, Carole
Figueiredo, Ana F.
Luna Cornadó, Jeroni
Fillat i Fonts, Cristina
Arbonés de Rafael, Maria Lourdes, 1959-
Graupera i Garcia-Milà, Mariona
Valverde, Miguel Ángel
Luna, Susana de la
author Rozen, Esteban J.
author_facet Rozen, Esteban J.
Roewenstrunk, Julia
Barallobre, María José
Di Vona, Chiara
Jung, Carole
Figueiredo, Ana F.
Luna Cornadó, Jeroni
Fillat i Fonts, Cristina
Arbonés de Rafael, Maria Lourdes, 1959-
Graupera i Garcia-Milà, Mariona
Valverde, Miguel Ángel
Luna, Susana de la
author_role author
author2 Roewenstrunk, Julia
Barallobre, María José
Di Vona, Chiara
Jung, Carole
Figueiredo, Ana F.
Luna Cornadó, Jeroni
Fillat i Fonts, Cristina
Arbonés de Rafael, Maria Lourdes, 1959-
Graupera i Garcia-Milà, Mariona
Valverde, Miguel Ángel
Luna, Susana de la
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Angiogènesi
Càncer
Neovascularization
Cancer
topic Angiogènesi
Càncer
Neovascularization
Cancer
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 PLC gamma 1 activation. Notably, Dyrk1 alpha heterozygous mice show defects in developmental retinal vascularization. Our data establish a regulatory circuit, DYRK1A/C-a2+/NFAT, to fine-tune endothelial cell proliferation and angiogenesis.
publishDate 2018
dc.date.none.fl_str_mv 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 https://hdl.handle.net/2445/172465
url https://hdl.handle.net/2445/172465
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1016/j.celrep.2018.04.008
Cell Reports, 2018, vol. 23, num. 6, Pp 1867-1878
https://doi.org/10.1016/j.celrep.2018.04.008
info:eu-repo/grantAgreement/EC/H2020/675392
info:eu-repo/grantAgreement/EC/FP7/317250
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Rozen et al., 2018
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Rozen et al., 2018
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300724

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