BMP-9 was initially isolated from fetal mouse liver cDNA libraries. The mouse and human proteins share 84% identity. They are part of the bone morphogenetic protein (BMP) family of proteins, which are members of the TGF-β superfamily and play a key role in skeletal development, bone formation, and stem cell differentiation. BMP-9 is one of the most osteogenic factors of the family. It is synthetized by hepatocytes and intrahepatic biliary epithelial cells. It circulates in plasma in an unprocessed, inactive form, that can be further activated by furin as well as a mature and fully active complex form bound to its prodomain. BMPs signal through heterotetrameric complex receptors, which include four type I receptors (ALK-1, ALK-2, ALK-3, and ALK-6) and three type II receptors (BMPRII, ActRIIA, and ActRIIB). BMP-9 and BMP-10 bind to ALK-1 (mainly expressed in endothelial cells). BMP-9 inhibits the proliferation of endothelial cells induced by basic FGF and VEGF-stimulated angiogenesis by binding to ALK-1. BMP-9 also binds to ALK-2 in primary myeloma cells, and this binding can be inhibited by membrane-bound or soluble endoglin (an accessory receptor for the TGF-β family). BMP-9 activity is inhibited by crossveinless-2 (CV2), a member of the chordin family and an extracellular regulator. BMP-9 induces CV2 expression in endothelial cells and in a negative feedback loop inhibits its own activity by the binding of CV2 to BMP-9, which consequently inhibits its binding to ALK-1. BMP-9 and -10 possess tumor suppressing activity in breast and prostate cancer; BMP-9 also induces apoptosis in primary myeloma cells. In contrast, autocrine BMP-9 signaling induces proliferation of ovarian and liver cancer cells.
Size
25 μg
Concentration
n/a
Applications
BA
Other Names
Bone morphogenetic protein 9 (BMP9), Growth/differentiation factor 2 (GDF2), GDF-2