ACVR1 Antibody #4398

Activin receptor type 1 (ACVR1), also known as activin receptor-like kinase 2 (ALK2), is a membrane-associated serine/threonine kinase receptor that binds activin A and related TGF-β superfamily growth factors, including bone morphogenetic protein 2 (BMP2), BMP4, BMP6, and BMP7 (1-3). Functional BMP receptor tetramers are composed of a pair of type I (ACVR1, ACVRL1, BMPR1A, or BMPR1B) and a pair of type II (BMPR2, ACVR2A, ACVR2B) receptor proteins (4). Following ligand binding, ACVR1 is phosphorylated by its type II binding partner, which allows recruitment and activation of receptor-regulated SMAD (R-Smad) proteins (5). Phosphorylation of R-Smad proteins results in their translocation to the nucleus, where R-Smads stimulate transcription of target genes (6). Mutations in the corresponding ACVR1 gene, including Arg206His (R206H) and Glu207Asp (Q207D), cause constitutive activation of the receptor and are associated with the genetic developmental disorders hereditary hemorrhagic telangiectasia and fibrodysplasia ossificans progressive (FOP) (7-11). In a mouse model of FOP, overexpression of the wild-type ACVR1 gene lessened the skeletal lesions associated with the R206H genetic background (12). Small molecule inhibitors of the ACVR1 kinase domain can disrupt downstream SMAD1/5 activation, offering a promising therapeutic avenue in FOP, cancers, or other disorders arising from gain-of-function ACVR1 mutations (13,14).