BMP-2 ELISA Kit, Rat

BMPs signal through type I and II serine/threonine kinase receptors that phosphorylate the downstream target proteins Smads. Activation of type I BMP receptor phosphorylates Smad1, Smad5, and presumably Smad8 and associates with Smad4 in a heteromeric complex that is translocated to the nucleus, where it activates transcription. TGF-beta binding to receptors leads to phosphorylated Smad2 and Smad3, which associate with Smad4, and the complex can translocate to the nucleus to regulate transcriptional activity. The Smad signaling pathway has been shown to play a role in BMP-2-induced osteoblast differentiation. However, other signaling pathways, such as extracellular signal-regulated kinase (ERK1/2), protein kinase C, and cAMP-dependent protein kinase A (PKA) may also be involved in the BMP-induced effects on bone cells. It was shown that PI-3 kinase/Akt pathway was involved in BMP-2 induced osteoblast differentiation.² Another cascade is activated by TGF-beta and BMP-4 and involves TGF-beta-activated kinase-1 (TAK1), a member of the mitogen-activated protein kinase (MAPK) kinase family, p38, and c-Jun N-terminal kinase. The TAK1-p38 kinase pathway was also found to be involved in BMP-2-induced apoptosis. It was also shown that that the BMP-2-induced apoptosis in human osteoblasts is mediated by activation of PKC, leading to activation of caspase-9, effector caspases, and DNA fragmentation.³ Moreover, BMP-2 mediates retinoid-induced apoptosis in medulloblastoma cells through a paracrine effect.⁴ Additionally, it was shown that BMP-2 signaling may cross-talk with Wnt signaling pathway in regulation of C2C12 cell differentiation.⁵