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
| Autores: | , , , , , |
|---|---|
| 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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| 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 |
| score |
15,812429 |