title: Dynamic phosphorylation of VE-cadherin Y685 throughout mouse estrous cycle in ovary and uterus.
abstract: We previously reported that vascular endothelial growth factor induced vascular endothelial (VE)-cadherin tyrosine phosphorylation at Y685 in a Src-dependent manner in vitro. Here, we studied the occurrence of Y685 phosphorylation in vivo in the female reproductive tract because it is a unique model of physiological vascular remodeling dependent on vascular endothelial growth factor. We first developed and characterized an anti-phospho-specific antibody against the site Y685 of VE-cadherin to monitor VE-cadherin phosphorylation along the four phases of mouse estrous cycle, termed proestrus, estrus, metestrus, and diestrus. A dynamic profile of tyrosine phosphorylated proteins was observed in both uterus and ovary throughout mouse estrous cycle, including kinase Src, which was found highly active at the estrus phase. The extent of tyrosine phosphorylated VE-cadherin was low at proestrus but strongly increased at estrus and returned to baseline at metestrus and diestrus, suggesting a potent hormonal regulation of this specific process. Indeed, C57Bl/6 female mice treatment with pregnant mare serum gonadotropin and human chorionic gonadotropin confirmed a significant increase in phosphoY685-VE-cadherin compared with that in untreated mice. These results demonstrate that VE-cadherin tyrosine phosphorylation at Y685 is a physiological and hormonally regulated process in female reproductive organs. In addition, this process was concomitant with the early steps of vascular remodeling taking place at estrus stage, suggesting that phosphoY685-VE-cadherin is a biomarker of endothelial cell activation in vivo.
authors.affiliation: INSERM, Unité 1036, Biology of Cancer and Infection, Grenoble, France; UJF-Grenoble 1, Biology of Cancer and Infection, Grenoble, France; CEA, DSV/iRTSV, Biology of Cancer and Infection, Grenoble, France; and.
authors.forename: Adama
authors.initials: A
authors.lastname: Sidibé
authors.affiliation: INSERM, Unité 1036, Biology of Cancer and Infection, Grenoble, France; UJF-Grenoble 1, Biology of Cancer and Infection, Grenoble, France; CEA, DSV/iRTSV, Biology of Cancer and Infection, Grenoble, France; and.
authors.forename: Helena
authors.initials: H
authors.lastname: Polena
authors.affiliation: INSERM, Unité 1036, Biology of Cancer and Infection, Grenoble, France; UJF-Grenoble 1, Biology of Cancer and Infection, Grenoble, France; CEA, DSV/iRTSV, Biology of Cancer and Infection, Grenoble, France; and.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Razanajatovo
authors.affiliation: INSERM, Unité 1036, Biology of Cancer and Infection, Grenoble, France; UJF-Grenoble 1, Biology of Cancer and Infection, Grenoble, France; CEA, DSV/iRTSV, Biology of Cancer and Infection, Grenoble, France; and.
authors.forename: Tiphaine
authors.initials: T
authors.lastname: Mannic
authors.affiliation: INSERM, Unité 1036, Biology of Cancer and Infection, Grenoble, France; UJF-Grenoble 1, Biology of Cancer and Infection, Grenoble, France; CEA, DSV/iRTSV, Biology of Cancer and Infection, Grenoble, France; and.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chaumontel
authors.affiliation: INSERM, Unité 1036, Biology of Cancer and Infection, Grenoble, France; UJF-Grenoble 1, Biology of Cancer and Infection, Grenoble, France; CEA, DSV/iRTSV, Biology of Cancer and Infection, Grenoble, France; and.
authors.forename: Soumalamaya
authors.initials: S
authors.lastname: Bama
authors.affiliation: INSERM, Unité 1036, Biology of Cancer and Infection, Grenoble, France; UJF-Grenoble 1, Biology of Cancer and Infection, Grenoble, France; CEA, DSV/iRTSV, Biology of Cancer and Infection, Grenoble, France; and.
authors.forename: Irène
authors.initials: I
authors.lastname: Maréchal
authors.affiliation: INSERM, Unité 1036, Biology of Cancer and Infection, Grenoble, France; UJF-Grenoble 1, Biology of Cancer and Infection, Grenoble, France; CEA, DSV/iRTSV, Biology of Cancer and Infection, Grenoble, France; and.
authors.forename: Philippe
authors.initials: P
authors.lastname: Huber
authors.affiliation: INSERM, Unité 1036, Biology of Cancer and Infection, Grenoble, France; UJF-Grenoble 1, Biology of Cancer and Infection, Grenoble, France; CEA, DSV/iRTSV, Biology of Cancer and Infection, Grenoble, France; and.
authors.forename: Danielle
authors.initials: D
authors.lastname: Gulino-Debrac
authors.affiliation: INSERM, Unité 1036, Biology of Cancer and Infection, Grenoble, France; UJF-Grenoble 1, Biology of Cancer and Infection, Grenoble, France; CEA, DSV/iRTSV, Biology of Cancer and Infection, Grenoble, France; and Division of Internal Medicine, Grenoble University Hospital, Grenoble, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Bouillet
authors.affiliation: INSERM, Unité 1036, Biology of Cancer and Infection, Grenoble, France; UJF-Grenoble 1, Biology of Cancer and Infection, Grenoble, France; CEA, DSV/iRTSV, Biology of Cancer and Infection, Grenoble, France; and ivilgrain@cea.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vilgrain
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D030762:Estrous Cycle / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006064:Gonadotropins, Equine / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D010053:Ovary / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D013997:Time Factors; D014443:Tyrosine; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*; D066253:Vascular Remodeling; D019061:src-Family Kinases / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D006063:Chorionic Gonadotropin; D006064:Gonadotropins, Equine; D014443:Tyrosine; D019061:src-Family Kinases; D000099152:Cadherin 5
keywords: VE-cadherin phosphorylation in vivo; angiogenesis; estrous cycle; tyrosine kinase; vascular remodeling