期刊
GROWTH FACTORS
卷 28, 期 5, 页码 318-328出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/08977191003766874
关键词
BMP-7; IGF-I; PKD; FRC cultures
资金
- University of Texas Health Science Center San Antonio
We previously showed that exogenous insulin-like growth factor-I (IGF-I) and bone morphogenetic protein-7 (BMP-7) synergistically stimulated osteoblast differentiation in fetal rat calvaria (FRC) cells. We have now shown that BMP-7 alone and the BMP-7 and IGF-I combination synergistically stimulated protein kinase D (PKD) phosphorylation at Ser744/748 and Ser916. Transfection of FRC cells with a constitutively active PKD stimulated marker expression, while transfection with a catalytically inactive PKD did not. Moreover, Go6976, which inhibits protein kinase C (PKC) alpha and beta 1, blocked PKD phosphorylation and the synergistic action of the BMP-7 and IGF-I combination on osteoblast differentiation, whereas Go6983, which inhibits PKC alpha, beta, gamma, delta, and zeta, did not. Our results suggest that the FRC cell differentiation induced by BMP-7 and the BMP-7 and IGF-I combination requires stimulation of PKD activity. Our results are consistent with a novel mechanism in which combined BMP-7 and IGF-I signaling activates upstream novel PKC(s), which then phosphorylates and activates PKD, leading to enhanced osteoblast differentiation.
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