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Title: DYRK1A Kinase Positively Regulates Angiogenic Responses in Endothelial Cells
Author: 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 A.
Luna, Susana de la
Keywords: Angiogènesi
Issue Date: 8-Jan-2018
Publisher: Cell Press
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 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.
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It is part of: Cell Reports, 2018, vol. 23, num. 6, Pp 1867-1878
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Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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