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...
| Autores: | , , , , , , , , , , , |
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| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2018 |
| País: | España |
| Recursos: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/172465 |
| Acesso em linha: | https://hdl.handle.net/2445/172465 |
| Access Level: | acceso abierto |
| Palavra-chave: | Angiogènesi Càncer Neovascularization Cancer |
| Resumo: | 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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