BMPR2 inhibits activin and BMP signaling via wild-type ALK2.

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