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Type 1 contains a glycine-serine-rich domain to be phosphorylated by type 2 kinase domain, initiating the signaling transduction pathway of the SMAD signaling cascade. [3] The wrist epitope motif on BMP-2 has a high-affinity binding site for BMPR-IA. The knuckle epitope motif on BMP-2 has a low-affinity binding site for BMPR-II. [4]
Bone morphogenetic proteins (BMPs) are a group of growth factors also known as cytokines and as metabologens. [1] Professor Marshall Urist and Professor Hari Reddi discovered their ability to induce the formation of bone and cartilage, BMPs are now considered to constitute a group of pivotal morphogenetic signals, orchestrating tissue architecture throughout the body.
The R-Smads consist of Smad1, Smad2, Smad3, Smad5 and Smad8/9, [3] and are involved in direct signaling from the TGF-B receptor. [4]Smad4 is the only known human Co-Smad, and has the role of partnering with R-Smads to recruit co-regulators to the complex.
BMP4 is also known to activate the ERK, JNK and p38 MAPK signalling pathways whilst have been found to act independently of Smad signaling pathways, are mostly active in conjunction with Smad. [32] The activation of the ERK and JNK pathways acts to phosphorylate Smad and therefore regulate its activation.
BMPR1B is a member of the bone morphogenetic protein (BMP) receptor family of transmembrane serine/threonine kinases. The ligands of this receptor are BMPs, which are members of the TGF-beta superfamily. BMPs are involved in endochondral bone formation and embryogenesis.
BMPR2 is expressed on both human and animal granulosa cells, and is a crucial receptor for bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9). ). These two protein signaling molecules and their BMPR2-mediated effects play an important role in follicle development in preparation for ovulatio
Repulsive guidance molecule A (RGMa) is a bone morphogenetic protein (BMP) co-receptor of the repulsive guidance molecule family. Together with BMPR1A and BMPR1B, as well as ACVR2A and BMPR2, it binds BMPs thereby activating the intracellular SMAD1/5/8 signalling pathway. [5] In humans this protein is encoded by the RGMA gene. [6]
The activin type 2 receptors belong to a larger TGF-beta receptor family and modulate signals for transforming growth factor beta ligands. These receptors are involved in a host of physiological processes including, growth, cell differentiation, homeostasis, osteogenesis, apoptosis and many other functions.