Involvement of MAPK signaling molecules and Runx2 in the NELL1-induced osteoblastic differentiation

被引:75
作者
Bokui, Nobuyuki [1 ]
Otani, Takayuki [2 ]
Igarashi, Koichi [2 ]
Kaku, Junichiro [3 ]
Oda, Mitsuo [4 ]
Nagaoka, Tadahiro [5 ]
Seno, Masaharu [5 ]
Taternatsu, Kenji
Okajima, Toshihide [1 ]
Matsuzaki, Takashi [1 ]
Ting, Kang [6 ,7 ]
Tanizawa, Katsuyuki [1 ]
Kuroda, Shunichi [1 ]
机构
[1] Osaka Univ, Inst Sci & Ind Res, Dept Struct Mol Biol, Osaka 5670047, Japan
[2] Katayama Chem Ind Co Ltd, Osaka 5620015, Japan
[3] Hirai Dent Clin, Tokyo 1320035, Japan
[4] Showa Univ, Sch Dent, Tokyo 1428555, Japan
[5] Okayama Univ, Grad Sch Nat Sci & Technol, Okayama 7008530, Japan
[6] Univ Calif Los Angeles, Sch Engn, Dept Biomed Engn, Los Angeles, CA 90095 USA
[7] Univ Calif Los Angeles, Sch Dent, Sect Orthodont, Los Angeles, CA 90095 USA
关键词
MAP kinase; osteoblast; differentiation; bone; tyrosine phosphorylation;
D O I
10.1016/j.febslet.2007.12.006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
NELL1 is an extracellular protein inducing osteogenic differentiation and bone formation of osteoblastic cells. To elucidate the intracellular signaling cascade evoked by NELL1, we have shown that NELL1 protein transiently activates the MAPK signaling cascade, induces the phosphorylation of Runx2, and promotes the rapid intracellular accumulation of Tyr-phosphorylated proteins. Unlike BMP2, NELL1 protein does not activate the Smad signaling cascade. These findings suggest that upon binding to a specific receptor NELL1 transduces an osteogenic signal through activation of certain Tyr-kinases associated with the Ras-MAPK cascade, and finally leads to the osteogenic differentiation. (C) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:365 / 371
页数:7
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