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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Detalles Bibliográficos
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
Descripción
Sumario: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.

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