Activation of signalling by the activin receptor complex Journal Article
| Authors: | Attisano, L.; Wrana, J. L.; Montalvo, E.; Massagué, J. |
| Article Title: | Activation of signalling by the activin receptor complex |
| Abstract: | Activin exerts its effects by simultaneously binding to two types of protein 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-IB and -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. |
| Keywords: | signal transduction; protein phosphorylation; mutation; nonhuman; animal cell; animals; cell line; transfection; protein serine threonine kinase; animalia; amino acid sequence; molecular sequence data; protein-serine-threonine kinases; growth regulation; ligands; mink; receptors, growth factor; receptor subtype; hormone receptor interaction; activin; priority journal; article; mustela vison; activin receptors |
| Journal Title: | Molecular and Cellular Biology |
| Volume: | 16 |
| Issue: | 3 |
| ISSN: | 0270-7306 |
| Publisher: | American Society for Microbiology |
| Date Published: | 1996-03-01 |
| Start Page: | 1066 |
| End Page: | 1073 |
| Language: | English |
| PUBMED: | 8622651 |
| PROVIDER: | scopus |
| PMCID: | PMC231089 |
| DOI: | 10.1128/MCB.16.3.1066 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
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