The orphan ligand, activin C, signals through activin receptor-like kinase 7.
Activin
Activin C
Adipocyte
Signaling
activin-like kinase 7
biochemistry
chemical biology
human
mouse
transforming growth factor beta
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
23 06 2022
23 06 2022
Historique:
received:
26
02
2022
accepted:
09
06
2022
entrez:
23
6
2022
pubmed:
24
6
2022
medline:
28
6
2022
Statut:
epublish
Résumé
Activin ligands are formed from two disulfide-linked inhibin β (Inhβ) subunit chains. They exist as homodimeric proteins, as in the case of activin A (ActA; InhβA/InhβA) or activin C (ActC; InhβC/InhβC), or as heterodimers, as with activin AC (ActAC; InhβA:InhβC). While the biological functions of ActA and activin B (ActB) have been well characterized, little is known about the biological functions of ActC or ActAC. One thought is that the InhβC chain functions to interfere with ActA production by forming less active ActAC heterodimers. Here, we assessed and characterized the signaling capacity of ligands containing the InhβC chain. ActC and ActAC activated SMAD2/3-dependent signaling via the type I receptor, activin receptor-like kinase 7 (ALK7). Relative to ActA and ActB, ActC exhibited lower affinity for the cognate activin type II receptors and was resistant to neutralization by the extracellular antagonist, follistatin. In mature murine adipocytes, which exhibit high ALK7 expression, ActC elicited a SMAD2/3 response similar to ActB, which can also signal via ALK7. Collectively, these results establish that ActC and ActAC are active ligands that exhibit a distinct signaling receptor and antagonist profile compared to other activins.
Identifiants
pubmed: 35736809
doi: 10.7554/eLife.78197
pii: 78197
pmc: PMC9224996
doi:
pii:
Substances chimiques
Ligands
0
Activins
104625-48-1
Activin Receptors
EC 2.7.11.30
Activin Receptors, Type I
EC 2.7.11.30
Acvr1c protein, mouse
EC 2.7.11.30
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM134923
Pays : United States
Informations de copyright
© 2022, Goebel et al.
Déclaration de conflit d'intérêts
EG, LO, EK, KV, DB, TT No competing interests declared, EB, RC, RK Past employee of Acceleron Pharma and is now an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc
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