Bone morphogenetic protein receptor type-1B (BMPR-IB) (BMPR-IB)

Bone morphogenetic protein receptor type-1B (BMPR-IB), also known as ALK-6, is a transmembrane serine/threonine kinase that serves as a type I receptor for the bone morphogenetic protein (BMP) signaling pathway [UniProt, https://www.uniprot.org/uniprotkb/O00238/entry; Wikipedia, https://en.wikipedia.org/wiki/BMPR1B]. It plays a critical role in skeletal development, particularly in the formation of the phalanges and joints, and is essential for ovarian follicle development and ovulation [NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820739/]. In the canonical signaling pathway, BMPR-IB forms a heterotetrameric complex with type II receptors upon ligand binding (such as BMP-2, BMP-4, or GDF-5), leading to the phosphorylation of SMAD 1, 5, and 8, which then regulate the transcription of genes involved in cell differentiation and proliferation [NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990394/]. Mutations in the BMPR1B gene are linked to various skeletal dysplasias, including brachydactyly and acromesomelic dysplasia, and have been implicated in the regulation of prolificacy in livestock [UniProt, https://www.uniprot.org/uniprotkb/O00238/entry]. In oncology, BMPR-IB exhibits a dual role, acting as a tumor promoter in certain cancers like ovarian and breast cancer, while functioning as a tumor suppressor in others such as glioblastoma [NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313701/]. Although no drugs specifically targeting BMPR-IB are currently FDA-approved, small molecule inhibitors like LDN-193189 are widely used in research to study its therapeutic potential in cancer and fibrotic diseases [Guide to Pharmacology, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1789].

Other names

ALK-6ALK6CDw293AMDDBDA1DBDA2AMD3Acvrlk6SKR6Bone morphogenetic protein receptor type 1B

Inhibition of intracellular serine/threonine kinase activity, blockade of SMAD 1/5/8 phosphorylation, and antagonism of BMP ligand binding.