Activins as Dual Specificity TGF-β Family Molecules: SMAD-Activation via Activin- and BMP-Type 1 Receptors.
ACVR1
ALK2
BMP
SMAD
activin
signal transduction
Journal
Biomolecules
ISSN: 2218-273X
Titre abrégé: Biomolecules
Pays: Switzerland
ID NLM: 101596414
Informations de publication
Date de publication:
29 03 2020
29 03 2020
Historique:
received:
19
02
2020
revised:
25
03
2020
accepted:
27
03
2020
entrez:
3
4
2020
pubmed:
3
4
2020
medline:
30
3
2021
Statut:
epublish
Résumé
Activins belong to the transforming growth factor (TGF)-β family of multifunctional cytokines and signal via the activin receptors ALK4 or ALK7 to activate the SMAD2/3 pathway. In some cases, activins also signal via the bone morphogenetic protein (BMP) receptor ALK2, causing activation of the SMAD1/5/8 pathway. In this study, we aimed to dissect how activin A and activin B homodimers, and activin AB and AC heterodimers activate the two main SMAD branches. We compared the activin-induced signaling dynamics of ALK4/7-SMAD2/3 and ALK2-SMAD1/5 in a multiple myeloma cell line. Signaling via the ALK2-SMAD1/5 pathway exhibited greater differences between ligands than signaling via ALK4/ALK7-SMAD2/3. Interestingly, activin B and activin AB very potently activated SMAD1/5, resembling the activation commonly seen with BMPs. As SMAD1/5 was also activated by activins in other cell types, we propose that dual specificity is a general mechanism for activin ligands. In addition, we found that the antagonist follistatin inhibited signaling by all the tested activins, whereas the antagonist cerberus specifically inhibited activin B. Taken together, we propose that activins may be considered dual specificity TGF-β family members, critically affecting how activins may be considered and targeted clinically.
Identifiants
pubmed: 32235336
pii: biom10040519
doi: 10.3390/biom10040519
pmc: PMC7225989
pii:
doi:
Substances chimiques
Smad Proteins
0
Transforming Growth Factor beta
0
activin A
0
activin B
0
Activins
104625-48-1
ACVR1 protein, human
EC 2.7.11.30
Activin Receptors, Type I
EC 2.7.11.30
Bone Morphogenetic Protein Receptors, Type I
EC 2.7.11.30
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM121499
Pays : United States
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