The EGF-like proteins DLK1 and DLK2 function as inhibitory non-canonical ligands of NOTCH1 receptor that modulate each others activities

The protein DLK2, highly homologous to DLK1, belongs to the EGF-like family of membrane proteins, which includes NOTCH receptors and their DSL-ligands. The molecular mechanisms by which DLK proteins regulate cell differentiation and proliferation processes are not fully established yet. In previous...

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Autores: Sánchez Solana, Beatriz, Nueda Sanz, María Luisa, Ruvira Garrigues, María Desamparados, Ruiz Hidalgo, María José, Monsalve Argandoña, Eva María, Rivero Hinojosa, Samuel, García Ramírez, José Javier, Martínez Díaz-Guerra, María José, Baladrón García, Victoriano, Laborda Fernández, Jorge
Tipo de recurso: artículo
Fecha de publicación:2011
País:España
Institución:Fundación Dialnet. Universidad de La Rioja
Repositorio:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/47981
Acceso en línea:https://hdl.handle.net/10578/47981
Access Level:acceso abierto
Palabra clave:DLK1
DLK2
NOTCH canonical ligand
NOTCH signaling
Protein–protein interaction
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spelling The EGF-like proteins DLK1 and DLK2 function as inhibitory non-canonical ligands of NOTCH1 receptor that modulate each others activitiesSánchez Solana, BeatrizNueda Sanz, María LuisaRuvira Garrigues, María DesamparadosRuiz Hidalgo, María JoséMonsalve Argandoña, Eva MaríaRivero Hinojosa, SamuelGarcía Ramírez, José JavierMartínez Díaz-Guerra, María JoséBaladrón García, VictorianoLaborda Fernández, JorgeDLK1DLK2NOTCH canonical ligandNOTCH signalingProtein–protein interactionThe protein DLK2, highly homologous to DLK1, belongs to the EGF-like family of membrane proteins, which includes NOTCH receptors and their DSL-ligands. The molecular mechanisms by which DLK proteins regulate cell differentiation and proliferation processes are not fully established yet. In previous reports, we demonstrated that DLK1 interacts with itself and with specific EGF-like repeats of the NOTCH1 extracellular region involved in the binding to NOTCH1 canonical ligands. Moreover, the interaction of DLK1 with NOTCH1 caused an inhibition of basal NOTCH signaling in preadipocytes and mesenchymal multipotent cells. In this work, we demonstrate, for the first time, that DLK2 interacts with itself, with DLK1, and with the same NOTCH1 receptor region as DLK1 does. We demonstrate also that the interaction of DLK2 with NOTCH1 similarly results in an inhibition of NOTCH signaling in preadipocytes and Mouse Embryo fibloblasts. In addition, we demonstrate that a membrane DLK1 variant, lacking the sequence recognized by the protease TACE, also inhibits NOTCH signaling. Furthermore, both DLK1 and DLK2 are able to decrease NOTCH activity also when triggered by specific NOTCH ligands. However, the decrease in NOTCH signaling induced by overexpression of Dlk2 is reversed by the overexpression of Dlk1, and viceversa. We conclude that DLK1 and DLK2 act as inhibitory non-canonical protein ligands for the NOTCH1 receptor that modulate NOTCH signaling.Elsevier202620262011info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://hdl.handle.net/10578/47981reponame:RUIdeRA. Repositorio Institucional de la UCLMinstname:Fundación Dialnet. Universidad de La RiojaInglésSAN06-014PII1I09-0164-00BFU2007-61094/BMCinfo:eu-repo/semantics/openAccessoai:ruidera.uclm.es:10578/479812026-05-27T07:36:41Z
dc.title.none.fl_str_mv The EGF-like proteins DLK1 and DLK2 function as inhibitory non-canonical ligands of NOTCH1 receptor that modulate each others activities
title The EGF-like proteins DLK1 and DLK2 function as inhibitory non-canonical ligands of NOTCH1 receptor that modulate each others activities
spellingShingle The EGF-like proteins DLK1 and DLK2 function as inhibitory non-canonical ligands of NOTCH1 receptor that modulate each others activities
Sánchez Solana, Beatriz
DLK1
DLK2
NOTCH canonical ligand
NOTCH signaling
Protein–protein interaction
title_short The EGF-like proteins DLK1 and DLK2 function as inhibitory non-canonical ligands of NOTCH1 receptor that modulate each others activities
title_full The EGF-like proteins DLK1 and DLK2 function as inhibitory non-canonical ligands of NOTCH1 receptor that modulate each others activities
title_fullStr The EGF-like proteins DLK1 and DLK2 function as inhibitory non-canonical ligands of NOTCH1 receptor that modulate each others activities
title_full_unstemmed The EGF-like proteins DLK1 and DLK2 function as inhibitory non-canonical ligands of NOTCH1 receptor that modulate each others activities
title_sort The EGF-like proteins DLK1 and DLK2 function as inhibitory non-canonical ligands of NOTCH1 receptor that modulate each others activities
dc.creator.none.fl_str_mv Sánchez Solana, Beatriz
Nueda Sanz, María Luisa
Ruvira Garrigues, María Desamparados
Ruiz Hidalgo, María José
Monsalve Argandoña, Eva María
Rivero Hinojosa, Samuel
García Ramírez, José Javier
Martínez Díaz-Guerra, María José
Baladrón García, Victoriano
Laborda Fernández, Jorge
author Sánchez Solana, Beatriz
author_facet Sánchez Solana, Beatriz
Nueda Sanz, María Luisa
Ruvira Garrigues, María Desamparados
Ruiz Hidalgo, María José
Monsalve Argandoña, Eva María
Rivero Hinojosa, Samuel
García Ramírez, José Javier
Martínez Díaz-Guerra, María José
Baladrón García, Victoriano
Laborda Fernández, Jorge
author_role author
author2 Nueda Sanz, María Luisa
Ruvira Garrigues, María Desamparados
Ruiz Hidalgo, María José
Monsalve Argandoña, Eva María
Rivero Hinojosa, Samuel
García Ramírez, José Javier
Martínez Díaz-Guerra, María José
Baladrón García, Victoriano
Laborda Fernández, Jorge
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DLK1
DLK2
NOTCH canonical ligand
NOTCH signaling
Protein–protein interaction
topic DLK1
DLK2
NOTCH canonical ligand
NOTCH signaling
Protein–protein interaction
description The protein DLK2, highly homologous to DLK1, belongs to the EGF-like family of membrane proteins, which includes NOTCH receptors and their DSL-ligands. The molecular mechanisms by which DLK proteins regulate cell differentiation and proliferation processes are not fully established yet. In previous reports, we demonstrated that DLK1 interacts with itself and with specific EGF-like repeats of the NOTCH1 extracellular region involved in the binding to NOTCH1 canonical ligands. Moreover, the interaction of DLK1 with NOTCH1 caused an inhibition of basal NOTCH signaling in preadipocytes and mesenchymal multipotent cells. In this work, we demonstrate, for the first time, that DLK2 interacts with itself, with DLK1, and with the same NOTCH1 receptor region as DLK1 does. We demonstrate also that the interaction of DLK2 with NOTCH1 similarly results in an inhibition of NOTCH signaling in preadipocytes and Mouse Embryo fibloblasts. In addition, we demonstrate that a membrane DLK1 variant, lacking the sequence recognized by the protease TACE, also inhibits NOTCH signaling. Furthermore, both DLK1 and DLK2 are able to decrease NOTCH activity also when triggered by specific NOTCH ligands. However, the decrease in NOTCH signaling induced by overexpression of Dlk2 is reversed by the overexpression of Dlk1, and viceversa. We conclude that DLK1 and DLK2 act as inhibitory non-canonical protein ligands for the NOTCH1 receptor that modulate NOTCH signaling.
publishDate 2011
dc.date.none.fl_str_mv 2011
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10578/47981
url https://hdl.handle.net/10578/47981
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv SAN06-014
PII1I09-0164-00
BFU2007-61094/BMC
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:RUIdeRA. Repositorio Institucional de la UCLM
instname:Fundación Dialnet. Universidad de La Rioja
instname_str Fundación Dialnet. Universidad de La Rioja
reponame_str RUIdeRA. Repositorio Institucional de la UCLM
collection RUIdeRA. Repositorio Institucional de la UCLM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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