Fig. 5

Proposed regulation of ligand dependent ALK2 activity in multiple myeloma cells. A ALK2 ligands such as BMP6, BMP9, and activin B signal via ALK2 preferably in complex with ACVR2A or ACVR2B. Activin A also binds to ALK2:ACVR2 but may either form a non-signaling complex (NSC) or an active signaling complex depending on the context. Addition of FK506 removes FKBP12 from the activation domain of ALK2 leading to increased ligand-induced SMAD1/5-activation. SMAD1/5-activation leads to myeloma cell apoptosis. B ALK3 ligands such as BMP2, BMP4, and BMP10, do not activate SMAD1/5 via ALK2 even in the presence of their preferred type II receptor BMPR2. It is unclear if the ligand can form an NSC with the receptors or not. Addition of FK506 removes FKBP12 from the activation domain of ALK2 leading to a dose-dependent ligand-induced SMAD1/5-activation and myeloma cell apoptosis. The figure was made with Biorender.com