Cargando…
Activin E is a TGFβ ligand that signals specifically through activin receptor-like kinase 7
Activins are one of the three distinct subclasses within the greater Transforming Growth Factor β (TGFβ) superfamily. First discovered for their critical roles in reproductive biology, activins have since been shown to alter cellular differentiation and proliferation. At present, members of the acti...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10557571/ https://www.ncbi.nlm.nih.gov/pubmed/37808681 http://dx.doi.org/10.1101/2023.09.25.559288 |
_version_ | 1785117117673111552 |
---|---|
author | Vestal, Kylie A Kattamuri, Chandramohan Koyiloth, Muhasin Ongaro, Luisina Howard, James A Deaton, Aimee Ticau, Simina Dubey, Aditi Bernard, Daniel J Thompson, Thomas B |
author_facet | Vestal, Kylie A Kattamuri, Chandramohan Koyiloth, Muhasin Ongaro, Luisina Howard, James A Deaton, Aimee Ticau, Simina Dubey, Aditi Bernard, Daniel J Thompson, Thomas B |
author_sort | Vestal, Kylie A |
collection | PubMed |
description | Activins are one of the three distinct subclasses within the greater Transforming Growth Factor β (TGFβ) superfamily. First discovered for their critical roles in reproductive biology, activins have since been shown to alter cellular differentiation and proliferation. At present, members of the activin subclass include activin A (ActA), ActB, ActC, ActE, and the more distant members myostatin and GDF11. While the biological roles and signaling mechanisms of most activins class members have been well-studied, the signaling potential of ActE has remained largely unknown. Here, we characterized the signaling capacity of homodimeric ActE. Molecular modeling of the ligand:receptor complexes showed that ActC and ActE shared high similarity in both the type I and type II receptor binding epitopes. ActE signaled specifically through ALK7, utilized the canonical activin type II receptors, ActRIIA and ActRIIB, and was resistant to the extracellular antagonists follistatin and WFIKKN. In mature murine adipocytes, ActE invoked a SMAD2/3 response via ALK7, similar to ActC. Collectively, our results establish ActE as an ALK7 ligand, thereby providing a link between genetic and in vivo studies of ActE as a regulator of adipose tissue. |
format | Online Article Text |
id | pubmed-10557571 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-105575712023-10-07 Activin E is a TGFβ ligand that signals specifically through activin receptor-like kinase 7 Vestal, Kylie A Kattamuri, Chandramohan Koyiloth, Muhasin Ongaro, Luisina Howard, James A Deaton, Aimee Ticau, Simina Dubey, Aditi Bernard, Daniel J Thompson, Thomas B bioRxiv Article Activins are one of the three distinct subclasses within the greater Transforming Growth Factor β (TGFβ) superfamily. First discovered for their critical roles in reproductive biology, activins have since been shown to alter cellular differentiation and proliferation. At present, members of the activin subclass include activin A (ActA), ActB, ActC, ActE, and the more distant members myostatin and GDF11. While the biological roles and signaling mechanisms of most activins class members have been well-studied, the signaling potential of ActE has remained largely unknown. Here, we characterized the signaling capacity of homodimeric ActE. Molecular modeling of the ligand:receptor complexes showed that ActC and ActE shared high similarity in both the type I and type II receptor binding epitopes. ActE signaled specifically through ALK7, utilized the canonical activin type II receptors, ActRIIA and ActRIIB, and was resistant to the extracellular antagonists follistatin and WFIKKN. In mature murine adipocytes, ActE invoked a SMAD2/3 response via ALK7, similar to ActC. Collectively, our results establish ActE as an ALK7 ligand, thereby providing a link between genetic and in vivo studies of ActE as a regulator of adipose tissue. Cold Spring Harbor Laboratory 2023-09-25 /pmc/articles/PMC10557571/ /pubmed/37808681 http://dx.doi.org/10.1101/2023.09.25.559288 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Vestal, Kylie A Kattamuri, Chandramohan Koyiloth, Muhasin Ongaro, Luisina Howard, James A Deaton, Aimee Ticau, Simina Dubey, Aditi Bernard, Daniel J Thompson, Thomas B Activin E is a TGFβ ligand that signals specifically through activin receptor-like kinase 7 |
title | Activin E is a TGFβ ligand that signals specifically through activin receptor-like kinase 7 |
title_full | Activin E is a TGFβ ligand that signals specifically through activin receptor-like kinase 7 |
title_fullStr | Activin E is a TGFβ ligand that signals specifically through activin receptor-like kinase 7 |
title_full_unstemmed | Activin E is a TGFβ ligand that signals specifically through activin receptor-like kinase 7 |
title_short | Activin E is a TGFβ ligand that signals specifically through activin receptor-like kinase 7 |
title_sort | activin e is a tgfβ ligand that signals specifically through activin receptor-like kinase 7 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10557571/ https://www.ncbi.nlm.nih.gov/pubmed/37808681 http://dx.doi.org/10.1101/2023.09.25.559288 |
work_keys_str_mv | AT vestalkyliea activineisatgfbligandthatsignalsspecificallythroughactivinreceptorlikekinase7 AT kattamurichandramohan activineisatgfbligandthatsignalsspecificallythroughactivinreceptorlikekinase7 AT koyilothmuhasin activineisatgfbligandthatsignalsspecificallythroughactivinreceptorlikekinase7 AT ongaroluisina activineisatgfbligandthatsignalsspecificallythroughactivinreceptorlikekinase7 AT howardjamesa activineisatgfbligandthatsignalsspecificallythroughactivinreceptorlikekinase7 AT deatonaimee activineisatgfbligandthatsignalsspecificallythroughactivinreceptorlikekinase7 AT ticausimina activineisatgfbligandthatsignalsspecificallythroughactivinreceptorlikekinase7 AT dubeyaditi activineisatgfbligandthatsignalsspecificallythroughactivinreceptorlikekinase7 AT bernarddanielj activineisatgfbligandthatsignalsspecificallythroughactivinreceptorlikekinase7 AT thompsonthomasb activineisatgfbligandthatsignalsspecificallythroughactivinreceptorlikekinase7 |