Bone morphogenetic protein–Smad signaling pathway (BMP–Smad pathway)

The Bone morphogenetic protein–Smad signaling pathway is a highly conserved signal transduction cascade critical for regulating bone and cartilage formation, skeletal development, and tissue homeostasis. It is activated by bone morphogenetic proteins (BMPs), a subgroup of the transforming growth factor-beta (TGF-β) superfamily. Upon BMP binding, type I and type II serine/threonine kinase receptors dimerize and phosphorylate receptor-regulated Smad proteins (R-Smads: Smad1, Smad5, and Smad8). These R-Smads form complexes with the common-mediator Smad4, translocate to the nucleus, and regulate gene transcription involved in cell proliferation, differentiation, and apoptosis. The pathway is subject to feedback inhibition by inhibitory Smads (Smad6 and Smad7) and is also modulated by numerous non-canonical (Smad-independent) signals. Dysregulation contributes to developmental disorders, fibrosis, and cancer.

Other names

BMP/Smad pathwayBone morphogenetic protein signaling pathway (BMP pathway)BMP–Smad axisTGF-β/BMP–Smad pathway

Inhibitors of BMP receptors block phosphorylation of Smads, thus inhibiting downstream transcriptional events. Recombinant BMPs enhance osteogenesis by activating the pathway