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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorAlvarez-Palomo, Belén
dc.contributor.authorBarrot-Feixat, Carme
dc.contributor.authorSarret, Helena
dc.contributor.authorRequena, Jordi
dc.contributor.authorPau, Montserrat
dc.contributor.authorVidal Taboada, José Manuel
dc.date.accessioned2020-09-08T07:36:02Z
dc.date.available2020-09-08T07:36:02Z
dc.date.issued2019-10-08
dc.identifier.citationAlvarez-Palomo B, Barrot-Feixat C, Sarret H, Requena J, Pau M, Vidal-Taboada JM, et al. Two novel ligand-independent variants of the vegfr-1 receptorare expressed in human testis and spermatozoa, one of them with the ability to activate src proto-oncogene tyrosine kinases. Oncotarget. 2019 Oct 8;10(56):5871–87.
dc.identifier.issn1949-2553
dc.identifier.urihttp://hdl.handle.net/11351/5228
dc.descriptionSRC activation; Fertility; Mature testis
dc.description.abstractThe vascular endothelial growth factor receptor 1 (VEGFR-1) family of receptors is preferentially expressed in endothelial cells, with the full-length and mostly the soluble (sVEGFR-1) isoforms being the most expressed ones. Surprisingly, cancer cells (MDA-MB-231) express, instead, alternative intracellular VEGFR-1 variants. We wondered if these variants, that are no longer dependent on ligands for activation, were expressed in a physiological context, specifically in spermatogenic cells, and whether their expression was maintained in spermatozoa and required for human fertility. By interrogating a human library of mature testis cDNA, we characterized two new truncated intracellular variants different from the ones previously described in cancer cells. The new isoforms were transcribed from alternative transcription start sites (aTSS) located respectively in intron-19 (i19VEGFR-1) and intron-28 (i28VEGFR-1) of the VEGFR-1 gene (GenBank accession numbers JF509744 and JF509745) and expressed in mature testis and spermatozoa. In this paper, we describe the characterization of these isoforms by RT-PCR, northern blot, and western blot, their preferential expression in human mature testis and spermatozoa, and the elements that punctuate their proximal promoters and suggest cues for their expression in spermatogenic cells. Mechanistically, we show that i19VEGFR-1 has a strong ability to phosphorylate and activate SRC proto-oncogene non-receptor tyrosine kinases and a significant bias toward a decrease in expression in patients considered infertile by WHO criteria.
dc.language.isoeng
dc.publisherImpact Journals
dc.relation.ispartofseriesOncotarget;10(56)
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.sourceScientia
dc.subjectEsterilitat masculina
dc.subjectGenètica - Tècnica
dc.subjectEndoteli vascular
dc.subject.meshInfertility, Male
dc.subject.meshGenetic Techniques
dc.subject.meshVascular Endothelial Growth Factor Receptor-1
dc.titleTwo novel ligand-independent variants of the VEGFR-1 receptor are expressed in human testis and spermatozoa, one of them with the ability to activate SRC proto-oncogene tyrosine kinases
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.18632/oncotarget.27232
dc.subject.decsinfertilidad masculina
dc.subject.decstécnicas genéticas
dc.subject.decsreceptor 1 de factores de crecimiento endotelial vascular
dc.relation.publishversionhttps://www.oncotarget.com/article/27232/text/
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.authoraffiliation[Alvarez-Palomo B, Sarret H, Requena J] Molecular Genetics and Control of Pluripotency Laboratory, Department of Biomedicine, Biomedical Research Institute August Pi i Sunyer (IDIBAPS), Barcelona, Spain. Institute of Neurosciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain. [Barrot-Feixat C] Forensic Genetics Laboratory, Medicine Department, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain. [Pau M] Molecular Genetics Laboratory, Department of Biomedicine, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain. [Vidal-Taboada JM] Recerca en Sistema Nerviós Perifèric, Servei de Neurociència, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain
dc.identifier.pmid31645906
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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