dc.contributor
[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.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Barrot-Feixat, Carme
dc.contributor.author
Sarret, Helena
dc.contributor.author
Requena, Jordi
dc.contributor.author
Pau, Montserrat
dc.contributor.author
Vidal Taboada, José Manuel
dc.contributor.author
Alvarez-Palomo, Belén
dc.date.accessioned
2025-10-24T08:56:19Z
dc.date.available
2025-10-24T08:56:19Z
dc.date.issued
2020-09-08T07:36:02Z
dc.date.issued
2020-09-08T07:36:02Z
dc.date.issued
2019-10-08
dc.identifier
Alvarez-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
https://hdl.handle.net/11351/5228
dc.identifier
10.18632/oncotarget.27232
dc.identifier.uri
http://hdl.handle.net/11351/5228
dc.description.abstract
SRC activation; Fertility; Mature testis
dc.description.abstract
Activación de SRC; Fertilidad; Testículo maduro
dc.description.abstract
Activació SRC; Fertilitat; Testicle madur
dc.description.abstract
The 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.description.abstract
This study was supported by the University of Barcelona, MINECO project grant BFU2014-54467-P.
dc.format
application/pdf
dc.publisher
Impact Journals
dc.relation
Oncotarget;10(56)
dc.relation
https://www.oncotarget.com/article/27232/text/
dc.rights
Attribution-NonCommercial 4.0 International
dc.rights
http://creativecommons.org/licenses/by-nc/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Esterilitat masculina
dc.subject
Genètica - Tècnica
dc.subject
Endoteli vascular
dc.subject
DISEASES::Male Urogenital Diseases::Genital Diseases, Male::Infertility::Infertility, Male
dc.subject
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Genetic Techniques
dc.subject
CHEMICALS AND DRUGS::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases::Receptor Protein-Tyrosine Kinases::Receptors, Vascular Endothelial Growth Factor::Vascular Endothelial Growth Factor Receptor-1
dc.subject
ENFERMEDADES::enfermedades urogenitales masculinas::enfermedades de los genitales masculinos::infertilidad::infertilidad masculina
dc.subject
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::técnicas genéticas
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::enzimas y coenzimas::enzimas::transferasas::fosfotransferasas::fosfotransferasas (grupo alcohol aceptor)::proteína cinasas::proteína-tirosina cinasas::receptores proteína-tirosina cinasas::receptores del factor de crecimiento del endotelio vascular::receptor 1 de factores de crecimiento endotelial vascular
dc.title
Two 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.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
