BMPR1BALK6

BMPR1B, also known as activin receptor-like kinase 6 (ALK-6), is a receptor serine/threonine kinase that belongs to the bone morphogenetic protein (BMP) receptor type I family. The BMPR1B-ALK-6 protein is a single-pass transmembrane receptor that forms signaling complexes with type II BMP receptors on the cell surface. Upon binding BMP ligands, such as BMP2, BMP4, or BMP7, the constitutively active type II receptor phosphorylates the GS-rich activation loop of BMPR1B, activating its kinase activity.

This activation leads to phosphorylation of receptor-regulated SMAD proteins (SMAD1/5/8), which partner with SMAD4 and translocate to the nucleus to regulate target gene transcription. Non-SMAD signaling pathways may also be engaged, including MAPK cascades, contributing to a broader cellular response.

Physiological roles of BMPR1B signaling include regulation of skeletal development and homeostasis, with involvement in osteogenesis, chondrogenesis, and growth plate control. It also contributes to embryonic development and tissue repair processes, reflecting the diverse functions of BMP signaling in development and physiology.

Expression and regulation of BMPR1B are tissue-context dependent, with activity modulated by the availability of BMP ligands and extracellular antagonists such as noggin and chordin. Receptor activity is further regulated through endocytosis and degradation mechanisms that shape signaling dynamics.

Clinical relevance remains an area of active investigation. Alterations in BMPR1B signaling have been studied in relation to skeletal malformations and reproductive biology in humans and model organisms, but the full spectrum of associated phenotypes and their clinical significance is still being clarified.