PRL-2 phosphatase is required for vascular morphogenesis and angiogenic signaling

Autor: Poulet, Mathilde, Sirois, Jacinthe, Boyé, Kevin, Uetani, Noriko, Hardy, Serge, Daubon, Thomas, Dubrac, Alexandre, Tremblay, Michel, Bikfalvi, Andreas
Přispěvatelé: Laboratoire Angiogenèse et Micro-environnement des Cancers (LAMC), Université Sciences et Technologies - Bordeaux 1-Institut National de la Santé et de la Recherche Médicale (INSERM), McGill University = Université McGill [Montréal, Canada], Centre de recherche du CHU Sainte-Justine [Montreal], CHU Sainte Justine [Montréal]-Université de Montréal (UdeM), Université de Montréal (UdeM), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], DAUBON, Thomas
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Communications Biology
Communications Biology, Nature Publishing Group, 2020, 3 (1), ⟨10.1038/s42003-020-01343-z⟩
Communications Biology, Vol 3, Iss 1, Pp 1-14 (2020)
Communications Biology, 2020, 3 (1), ⟨10.1038/s42003-020-01343-z⟩
ISSN: 2399-3642
DOI: 10.1038/s42003-020-01343-z⟩
Popis: Protein tyrosine phosphatases are essential modulators of angiogenesis and have been identified as novel therapeutic targets in cancer and anti-angiogenesis. The roles of atypical Phosphatase of Regenerative Liver (PRL) phosphatases in this context remain poorly understood. Here, we investigate the biological function of PRL phosphatases in developmental angiogenesis in the postnatal mouse retina and in cell culture. We show that endothelial cells in the retina express PRL-2 encoded by the Ptp4a2 gene, and that inducible endothelial and global Ptp4a2 mutant mice exhibit defective retinal vascular outgrowth, arteriovenous differentiation, and sprouting angiogenesis. Mechanistically, PTP4A2 deletion limits angiogenesis by inhibiting endothelial cell migration and the VEGF-A, DLL-4/NOTCH-1 signaling pathway. This study reveals the importance of PRL-2 as a modulator of vascular development.
Poulet et al investigate the role for the PRL-2 phosphatase in mouse retina, and find that loss of PRL-2 impairs vascular outgrowth and arteriovenous patterning. They find that PRL-2 s regulates endothelial cell migration and sprouting angiogenesis and acts through VEGF and NOTCH1 signalling.
Databáze: OpenAIRE