Bone Morphogenetic Protein 2-induced MAPKs Activation Is Independent of the Smad1/5 Activation
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Bone morphogenetic protein (BMP) 2 is a potentosteogenic factor. Although both Smad1/5 and mitogenactivatedprotein kinases (MAPKs) are activated by BMP2,the hierarchical relationship between them is unclear. Inthis study, we examined if BMP2-stimulated MAPKactivation is regulated by Smad1/5 or vice versa. WhenC2C12 cells were treated with BMP2, the activation ofextracellular signal-regulated kinase (ERK), p38 MAPKand c-Jun-N-terminal kinase was evident within 5 min. Theknockdown of both Smad1 and Smad5 by small interferingRNA did not affect the activation of these MAPKs. Inaddition, neither the overexpression of Smad1 nor Smad5induced ERK activation. When ERK activation wasinduced by constitutively active MEK1 expression, theprotein level and activation of Smad1 increased. Furthermore, the inhibition of constitutively active BMPreceptor type IB-induced ERK activation significantlysuppressed Smad1 activation. These results indicate thatSmad1/5 activation is not necessary for BMP2-inducedMAPK activation and also that ERK positively regulatesSmad1 activation.
Abstract
Bone morphogenetic protein (BMP) 2 is a potentosteogenic factor. Although both Smad1/5 and mitogenactivatedprotein kinases (MAPKs) are activated by BMP2,the hierarchical relationship between them is unclear. Inthis study, we examined if BMP2-stimulated MAPKactivation is regulated by Smad1/5 or vice versa. WhenC2C12 cells were treated with BMP2, the activation ofextracellular signal-regulated kinase (ERK), p38 MAPKand c-Jun-N-terminal kinase was evident within 5 min. Theknockdown of both Smad1 and Smad5 by small interferingRNA did not affect the activation of these MAPKs. Inaddition, neither the overexpression of Smad1 nor Smad5induced ERK activation. When ERK activation wasinduced by constitutively active MEK1 expression, theprotein level and activation of Smad1 increased. Furthermore, the inhibition of constitutively active BMPreceptor type IB-induced ERK activation significantlysuppressed Smad1 activation. These results indicate thatSmad1/5 activation is not necessary for BMP2-inducedMAPK activation and also that ERK positively regulatesSmad1 activation.
참고문헌 (22)
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