Molecular mechanisms for activation of mutant activin receptor-like kinase 2 in fibrodysplasia ossificans progressiva

Publication date: Available online 13 April 2017
Source:Journal of Oral Biosciences
Author(s): Mai Fujimoto, Naoto Suda, Takenobu Katagiri
BackgroundFibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder characterized by progressive heterotopic ossification (HO) in soft tissues such as skeletal muscles, tendons, and ligaments. Gain-of-function mutations in ALK2, a type I receptor for bone morphogenetic proteins (BMPs), have been identified in patients with FOP; however, the molecular mechanisms that result in the activation of ALK2 mutants remain unclear.HighlightFOP-associated mutant ALK2 signaling is further enhanced by BMP type II receptor in a serine/threonine kinase activity-dependent manner. The threonine residue at position 203 (T203) in ALK2 is crucial for this enhancement by BMP type II receptor. Recently, activin A was found to be a critical ligand of ALK2 mutants.ConclusionBMP type II receptor-dependent phosphorylation of ALK2 mutants in response to ligand binding is important for the activation of BMP signaling in FOP. Therefore, the use of anti-activin A compounds would be a novel treatment approach for FOP.



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