Activation of Signalling by the Activin Receptor Complex
Open accessAbstract
Activin exerts its effects by simultaneously binding to two types of p rotein serine/threonine kinase receptors, each type existing in various isoforms. Using the ActR-IB and ActR-IIB receptor isoforms, we have investigated the mechanism of activin receptor activation. ActR-IIB are phosphoproteins with demonstrable affinity for each other. However, activin addition strongly promotes an interaction between these two proteins. Activin binds directly to ActR-IIB, and this complex associates with ActR-IB, which does not bind ligand on its own. In the resulting complex, ActR-IB becomes hyperphosphorylated, and this requires the kinase activity of ActR-IIB. Mutation of conserved serines and threonines in the GS domain, a region just upstream of the kinase domain in ActR-IB, abrogates both phosphorylation and signal propagation, suggesting that this domain contains phosphorylation sites required for signalling. ActR-IB activation can be mimicked by mutation of Thr-206 to aspartic acid, which yields a construct, ActR-IB(T206D), that signals in the absence of ligand. Furthermore, the signalling activity of this mutant construct is undisturbed by overexpression of a dominant negative kinase-defective ActR-IIB construct, indicating that ActR-IB(T206D) can signal independently of ActR-IIB. The evidence suggests that ActR-IIB acts as a primary activin receptor and ActR-IB acts as a downstream transducer of activin signals.
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Acvr1B is required for subsequent functional downstream signalling following recruitment by ligand-bound Acvr2.
“the receptor which is recruited by ligand-bound Acvr2 and which is required for subsequent functional downstream signalling33.”
From M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination (2013) · cites this paper as [33]
The Abstract says ligand-bound ActR-IIB associates with ActR-IB, and that ActR-IB acts as a downstream transducer whose GS-domain mutations abrogate signal propagation. This supports the recruitment and signalling mechanism, but the studied type II receptor is ActR-IIB, not the specifically named Acvr2. (LLM, conf=0.84)
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- Authors
- Attisano, L., Wrana, J. L., Montalvo, E., & Massagué, J.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1996-03-01
- Volume
- 16
- Issue
- 3
- Pages
- 1066-1073
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC231089
- OpenAlex
- W2103042473
- Cited by
- 316
- References
- 62
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 2 · 2023: 6 · 2022: 4 · 2021: 9 · 2020: 6 · 2019: 9 · 2018: 9 · 2017: 2 · 2016: 12 · 2015: 4 · 2014: 3 · 2013: 4 · 2012: 5
- FWCI
- 9.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA34610)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- activin signalling, receptor activation, receptor phosphorylation, receptor kinase activity, signal transduction
- MeSH terms
- Amino Acid Sequence, Animals, Cell Line, Ligands, Molecular Sequence Data, Mutation, Transfection, Signal Transduction, Protein Serine-Threonine Kinases, Receptors, Growth Factor, Activin Receptors
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