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

SRC activation; Fertility; Mature testis

Detalles Bibliográficos
Autores: Barrot-Feixat, Carme, Sarret, Helena, Requena, Jordi, Pau, Montserrat, Vidal Taboada, José Manuel, Alvarez-Palomo, Belén
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Departament de Salut de la Generalitat de Catalunya (DS)
Repositorio:Scientia. Dipòsit d'Informació Digital del Departament de Salut
OAI Identifier:oai:scientiasalut.gencat.cat:11351/5228
Acceso en línea:https://hdl.handle.net/11351/5228
Access Level:acceso abierto
Palabra clave:Esterilitat masculina
Genètica - Tècnica
Endoteli vascular
DISEASES::Male Urogenital Diseases::Genital Diseases, Male::Infertility::Infertility, Male
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Genetic Techniques
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
ENFERMEDADES::enfermedades urogenitales masculinas::enfermedades de los genitales masculinos::infertilidad::infertilidad masculina
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::técnicas genéticas
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
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oai_identifier_str oai:scientiasalut.gencat.cat:11351/5228
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv 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
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
spellingShingle 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
Barrot-Feixat, Carme
Esterilitat masculina
Genètica - Tècnica
Endoteli vascular
DISEASES::Male Urogenital Diseases::Genital Diseases, Male::Infertility::Infertility, Male
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Genetic Techniques
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
ENFERMEDADES::enfermedades urogenitales masculinas::enfermedades de los genitales masculinos::infertilidad::infertilidad masculina
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::técnicas genéticas
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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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.creator.none.fl_str_mv Barrot-Feixat, Carme
Sarret, Helena
Requena, Jordi
Pau, Montserrat
Vidal Taboada, José Manuel
Alvarez-Palomo, Belén
author Barrot-Feixat, Carme
author_facet Barrot-Feixat, Carme
Sarret, Helena
Requena, Jordi
Pau, Montserrat
Vidal Taboada, José Manuel
Alvarez-Palomo, Belén
author_role author
author2 Sarret, Helena
Requena, Jordi
Pau, Montserrat
Vidal Taboada, José Manuel
Alvarez-Palomo, Belén
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv [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
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Esterilitat masculina
Genètica - Tècnica
Endoteli vascular
DISEASES::Male Urogenital Diseases::Genital Diseases, Male::Infertility::Infertility, Male
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Genetic Techniques
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
ENFERMEDADES::enfermedades urogenitales masculinas::enfermedades de los genitales masculinos::infertilidad::infertilidad masculina
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::técnicas genéticas
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
topic Esterilitat masculina
Genètica - Tècnica
Endoteli vascular
DISEASES::Male Urogenital Diseases::Genital Diseases, Male::Infertility::Infertility, Male
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Genetic Techniques
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
ENFERMEDADES::enfermedades urogenitales masculinas::enfermedades de los genitales masculinos::infertilidad::infertilidad masculina
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::técnicas genéticas
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
description SRC activation; Fertility; Mature testis
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11351/5228
url https://hdl.handle.net/11351/5228
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Oncotarget;10(56)
https://www.oncotarget.com/article/27232/text/
dc.rights.none.fl_str_mv Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv Scientia
reponame:Scientia. Dipòsit d'Informació Digital del Departament de Salut
instname:Departament de Salut de la Generalitat de Catalunya (DS)
instname_str Departament de Salut de la Generalitat de Catalunya (DS)
reponame_str Scientia. Dipòsit d'Informació Digital del Departament de Salut
collection Scientia. Dipòsit d'Informació Digital del Departament de Salut
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869414045644226560
spelling 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 kinasesBarrot-Feixat, CarmeSarret, HelenaRequena, JordiPau, MontserratVidal Taboada, José ManuelAlvarez-Palomo, BelénEsterilitat masculinaGenètica - TècnicaEndoteli vascularDISEASES::Male Urogenital Diseases::Genital Diseases, Male::Infertility::Infertility, MaleANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Genetic TechniquesCHEMICALS 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-1ENFERMEDADES::enfermedades urogenitales masculinas::enfermedades de los genitales masculinos::infertilidad::infertilidad masculinaTÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::técnicas genéticasCOMPUESTOS 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 vascularSRC activation; Fertility; Mature testisActivación de SRC; Fertilidad; Testículo maduroActivació SRC; Fertilitat; Testicle madurThe 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.This study was supported by the University of Barcelona, MINECO project grant BFU2014-54467-P.Impact Journals[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, SpainVall d'Hebron Barcelona Hospital Campus202020202019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/11351/5228Scientiareponame:Scientia. Dipòsit d'Informació Digital del Departament de Salutinstname:Departament de Salut de la Generalitat de Catalunya (DS)InglésOncotarget;10(56)https://www.oncotarget.com/article/27232/text/Attribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:scientiasalut.gencat.cat:11351/52282026-06-12T09:38:37Z
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