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

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 intra...

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Autores: Álvarez Palomo, Ana Belén, Barrot i Feixat, Carme, Sarret, Helena, Requena Osete, Jordi, Pau, Montserrat, Vidal Taboada, José Manuel, Oliva Virgili, Rafael, Ballescà, Josep Lluís, Edel, Michael John, Mezquita Pla, Jovita
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/143063
Acceso en línea:https://hdl.handle.net/2445/143063
Access Level:acceso abierto
Palabra clave:Fecunditat humana
Espermatogènesi
Human fertility
Spermatogenesis
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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 kinasesÁlvarez Palomo, Ana BelénBarrot i Feixat, CarmeSarret, HelenaRequena Osete, JordiPau, MontserratVidal Taboada, José ManuelOliva Virgili, RafaelBallescà, Josep LluísEdel, Michael JohnMezquita Pla, JovitaFecunditat humanaEspermatogènesiHuman fertilitySpermatogenesisThe 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.Impact Journals2019201920192019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion17 p.application/pdfhttps://hdl.handle.net/2445/143063Articles publicats en revistes (Biomedicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.18632/oncotarget.27232Oncotarget, 2019, vol. 10, num. 56, p. 5871-5887https://doi.org/10.18632/oncotarget.27232cc-by (c) Álvarez Palomo, Ana Belén et al., 2019http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1430632026-05-29T05:05:01Z
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
Álvarez Palomo, Ana Belén
Fecunditat humana
Espermatogènesi
Human fertility
Spermatogenesis
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 Álvarez Palomo, Ana Belén
Barrot i Feixat, Carme
Sarret, Helena
Requena Osete, Jordi
Pau, Montserrat
Vidal Taboada, José Manuel
Oliva Virgili, Rafael
Ballescà, Josep Lluís
Edel, Michael John
Mezquita Pla, Jovita
author Álvarez Palomo, Ana Belén
author_facet Álvarez Palomo, Ana Belén
Barrot i Feixat, Carme
Sarret, Helena
Requena Osete, Jordi
Pau, Montserrat
Vidal Taboada, José Manuel
Oliva Virgili, Rafael
Ballescà, Josep Lluís
Edel, Michael John
Mezquita Pla, Jovita
author_role author
author2 Barrot i Feixat, Carme
Sarret, Helena
Requena Osete, Jordi
Pau, Montserrat
Vidal Taboada, José Manuel
Oliva Virgili, Rafael
Ballescà, Josep Lluís
Edel, Michael John
Mezquita Pla, Jovita
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Fecunditat humana
Espermatogènesi
Human fertility
Spermatogenesis
topic Fecunditat humana
Espermatogènesi
Human fertility
Spermatogenesis
description 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.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019
2019
2019
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/2445/143063
url https://hdl.handle.net/2445/143063
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.18632/oncotarget.27232
Oncotarget, 2019, vol. 10, num. 56, p. 5871-5887
https://doi.org/10.18632/oncotarget.27232
dc.rights.none.fl_str_mv cc-by (c) Álvarez Palomo, Ana Belén et al., 2019
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Álvarez Palomo, Ana Belén et al., 2019
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 17 p.
application/pdf
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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