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Involvement of p70 S6 kinase in bone morphogenetic protein signaling: Vascular endothelial growth factor synthesis by bone morphogenetic protein‐4 in osteoblasts
Author(s) -
Kozawa Osamu,
Matsuno Hiroyuki,
Uematsu Toshihiko
Publication year - 2001
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/1097-4644(20010601)81:3<430::aid-jcb1056>3.0.co;2-g
Subject(s) - bone morphogenetic protein 8a , bone morphogenetic protein 2 , bone morphogenetic protein 5 , bone morphogenetic protein 6 , microbiology and biotechnology , bone morphogenetic protein , p70 s6 kinase 1 , chemistry , vascular endothelial growth factor , bone morphogenetic protein 7 , signal transduction , biology , vegf receptors , cancer research , biochemistry , protein kinase b , gene , in vitro
In the present study, we investigated the effect of bone morphogenetic protein (BMP)‐4 on the synthesis of vascular endothelial growth factor (VEGF) in osteoblast‐like MC3T3‐E1 cells. BMP‐4 significantly stimulated VEGF synthesis time‐dependently up to 48 h. The stimulatory effect was dose‐dependent in the range between 1 and 100 ng/ml. BMP‐4 time‐dependently phosphorylated p70 S6 kinase. Rapamycin, an inhibitor of p70 S6 kinase, suppressed the BMP‐4‐stimulated VEGF synthesis as well as the phosphorylation of p70 S6 kinase. The VEGF synthesis by BMP‐4 was suppressed by wortmannin and LY294002, inhibitors of phosphatidylinositol 3‐kinase. Both wortmannin and LY294002 inhibited the BMP‐4‐stimulated phosphorylation of p70 S6 kinase. BMP‐4 did not affect the phosphorylation of Akt/protein kinase B. Taken together, our results strongly suggest that p70 S6 kinase takes part in BMP‐4‐stimulated VEGF synthesis as a positive regulator in osteoblasts and that phosphatidylinositol 3‐kinase acts at a point upstream from p70 S6 kinase. J. Cell. Biochem. 81:430–436, 2001. © 2001 Wiley‐Liss, Inc.