Rozen, 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 la2020-12-022020-12-022018-01-08https://hdl.handle.net/2445/172465Angiogenesis 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.13 p.application/pdfengcc-by-nc-nd (c) Rozen et al., 2018http://creativecommons.org/licenses/by-nc-nd/3.0/es/AngiogènesiCàncerNeovascularizationCancerinfo:eu-repo/semantics/article2020-12-02info:eu-repo/semantics/openAccess29742440