his.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
BMPR2 inhibits activin and BMP signaling via wild-type ALK2
Department of Clinical and Molecular Medicine, NTNU–Norwegian University of Science and Technology, Trondheim, Norway / Department of Hematology, St. Olav’s University Hospital, Trondheim, Norway.ORCID iD: 0000-0001-8922-5561
University of Skövde, School of Health and Education. University of Skövde, Health and Education. (Translational Medicine TRIM)ORCID iD: 0000-0001-7580-4570
Department of Clinical and Molecular Medicine, NTNU–Norwegian University of Science and Technology, Trondheim, Norway.
Department of Clinical and Molecular Medicine, NTNU–Norwegian University of Science and Technology, Trondheim, Norway.
Show others and affiliations
2018 (English)In: Journal of Cell Science, ISSN 0021-9533, E-ISSN 1477-9137, Vol. 131, no 11, article id UNSP jcs213512Article in journal (Refereed) Published
Abstract [en]

TGF-beta/BMP superfamily ligands require heteromeric complexes of type 1 and 2 receptors for ligand-dependent downstream signaling. Activin A, a TGF-beta superfamily member, inhibits growth of multiple myeloma cells, but the mechanism for this is unknown. We therefore aimed to clarify how activins affect myeloma cell survival. Activin A activates the transcription factors SMAD2/3 through the ALK4 type 1 receptor, but may also activate SMAD1/5/8 through mutated variants of the type 1 receptor ALK2 ( also known as ACVR1). We demonstrate that activin A and B activate SMAD1/5/8 in myeloma cells through endogenous wild-type ALK2. Knockdown of the type 2 receptor BMPR2 strongly potentiated activin A- and activin B-induced activation of SMAD1/5/8 and subsequent cell death. Furthermore, activity of BMP6, BMP7 or BMP9, which may also signal via ALK2, was potentiated by knockdown of BMPR2. Similar results were seen in HepG2 liver carcinoma cells. We propose that BMPR2 inhibits ALK2-mediated signaling by preventing ALK2 from oligomerizing with the type 2 receptors ACVR2A and ACVR2B, which are necessary for activation of ALK2 by activins and several BMPs. In conclusion, BMPR2 could be explored as a possible target for therapy in patients with multiple myeloma.

Place, publisher, year, edition, pages
2018. Vol. 131, no 11, article id UNSP jcs213512
Keywords [en]
Bone morphogenetic protein, BMPR2, ACVR2A, ACVR2B, Activin, ACVR1
National Category
Biological Sciences Basic Medicine Medical Biotechnology Cell and Molecular Biology
Research subject
Translational Medicine TRIM
Identifiers
URN: urn:nbn:se:his:diva-16198DOI: 10.1242/jcs.213512ISI: 000443414400008PubMedID: 29739878Scopus ID: 2-s2.0-85048313936OAI: oai:DiVA.org:his-16198DiVA, id: diva2:1247818
Available from: 2018-09-13 Created: 2018-09-13 Last updated: 2019-09-17Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMedScopus

Search in DiVA

By author/editor
Olsen, Oddrun EliseSankar, MeenuHolien, Toril
By organisation
School of Health and EducationHealth and Education
In the same journal
Journal of Cell Science
Biological SciencesBasic MedicineMedical BiotechnologyCell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 101 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf