title: Requirement of phosphorylatable endothelial nitric oxide synthase at Ser-1177 for vasoinhibin-mediated inhibition of endothelial cell migration and proliferation in vitro.
abstract: Endothelial nitric oxide synthase (eNOS)-derived nitric oxide is a major vasorelaxing factor and a mediator of vasopermeability and angiogenesis. Vasoinhibins, a family of antiangiogenic prolactin fragments that include 16 K prolactin, block most eNOS-mediated vascular effects. Vasoinhibins activate protein phosphatase 2A, causing eNOS inactivation through dephosphorylation of eNOS at serine residue 1179 in bovine endothelial cells and thereby blocking vascular permeability. In this study, we examined whether human eNOS phosphorylation at S1177 (analogous to bovine S1179) influences other actions of vasoinhibins. Bovine umbilical vein endothelial cells were stably transfected with human wild-type eNOS (WT) or with phospho-mimetic (S1177D) or non-phosphorylatable (S1177A) eNOS mutants. Vasoinhibins inhibited the increases in eNOS activity, migration, and proliferation following the overexpression of WT eNOS but did not affect these responses in cells expressing S1177D and S1177A eNOS mutants. We conclude that eNOS inhibition by dephosphorylation of S1177 is fundamental for the inhibition of endothelial cell migration and proliferation by vasoinhibins.
authors: Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus UNAM-Juriquilla, 76230, Querétaro, QRO, Mexico.
authors: Celina
authors: C
authors: García
authors: Rosa Elvira
authors: RE
authors: Nuñez-Anita
authors: Stéphanie
authors: S
authors: Thebault
authors: David
authors: D
authors: Arredondo Zamarripa
authors: Michael C
authors: MC
authors: Jeziorsky
authors: Gonzalo
authors: G
authors: Martínez de la Escalera
authors: Carmen
authors: C
authors: Clapp
mesh_terms: D000409:Alanine / Q000378:metabolism; D000818:Animals; D002417:Cattle; D018797:Cell Cycle Proteins / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D023421:Models, Animal; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D012694:Serine / Q000378:metabolism; D014162:Transfection
chemical_list: D018797:Cell Cycle Proteins; D011994:Recombinant Proteins; C493181:VASH1 protein, human; D012694:Serine; D052250:Nitric Oxide Synthase Type III; D000409:Alanine
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