Deregulated bone morphogenetic protein receptor signaling underlies fibrodysplasia ossificans progressiva.
Transforming growth factor-β family members, which include TGF-βs, activins and bone morphogenetic proteins (BMPs), play important roles in development and maintaining tissue homeostasis. The extracellular TGF-β family members signal across the plasmamembrane by activating type I and type II serine/threonine kinase receptors. Pertubation in TGF-β family receptor signaling has been implicated in certain diseases, including musculo-skeletal disorders. Fibrodysplasia ossificans progressiva (FOP) is a rare disorder characterized by progressive formation of ectopic bone and congenital malformations of the great toes. At present no curative therapy is available, therefore prevention of heterotopic ossification is the hallmark of FOP management. FOP has been linked to an autosomal dominant mutation on chromosome 2, to the gene encoding activin receptor-like kinase 2 (ALK2), a BMP type I receptor. This mutation is found in almost all classically affected FOP patients and causes the FOP phenotype. This discovery has paved the way for further investigations into the molecular basis underlying FOP and has recently pointed towards potential strategies to treat this devastating disease.
Department of Molecular Cell Biology, Leiden University Medical Center, The Netherlands.
David J J
DJ
de Gorter
Vishant
V
Jankipersadsing
Peter
P
Ten Dijke
D030201:Activin Receptors, Type I / Q000235:genetics*; D028341:Activins / Q000378:metabolism; D000818:Animals; D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D006801:Humans; D009154:Mutation; D009221:Myositis Ossificans / Q000235:genetics / Q000473:pathology*; D009999:Ossification, Heterotopic / Q000209:etiology / Q000517:prevention & control; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D019485:Bone Morphogenetic Proteins; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D028341:Activins; C425423:ACVR1 protein, human; D030201:Activin Receptors, Type I; D052004:Bone Morphogenetic Protein Receptors