Activin A inhibits BMP-signaling by binding ACVR2A and ACVR2B

Cell Commun Signal. 2015 Jun 6;13:27. doi: 10.1186/s12964-015-0104-z.

Abstract

Background: Activins are members of the TGF-β family of ligands that have multiple biological functions in embryonic stem cells as well as in differentiated tissue. Serum levels of activin A were found to be elevated in pathological conditions such as cachexia, osteoporosis and cancer. Signaling by activin A through canonical ALK4-ACVR2 receptor complexes activates the transcription factors SMAD2 and SMAD3. Activin A has a strong affinity to type 2 receptors, a feature that they share with some of the bone morphogenetic proteins (BMPs). Activin A is also elevated in myeloma patients with advanced disease and is involved in myeloma bone disease.

Results: In this study we investigated effects of activin A binding to receptors that are shared with BMPs using myeloma cell lines with well-characterized BMP-receptor expression and responses. Activin A antagonized BMP-6 and BMP-9, but not BMP-2 and BMP-4. Activin A was able to counteract BMPs that signal through the type 2 receptors ACVR2A and ACVR2B in combination with ALK2, but not BMPs that signal through BMPR2 in combination with ALK3 and ALK6.

Conclusions: We propose that one important way that activin A regulates cell behavior is by antagonizing BMP-ACVR2A/ACVR2B/ALK2 signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors, Type I / metabolism
  • Activin Receptors, Type II / metabolism*
  • Activins / metabolism*
  • Bone Morphogenetic Proteins / metabolism*
  • Cell Line, Tumor
  • Follistatin / metabolism
  • Humans
  • Multiple Myeloma / metabolism*
  • Protein Interaction Maps
  • Signal Transduction*

Substances

  • Bone Morphogenetic Proteins
  • Follistatin
  • activin A
  • Activins
  • ACVR1 protein, human
  • ACVR2B protein, human
  • Activin Receptors, Type I
  • Activin Receptors, Type II
  • activin receptor type II-A