Src enhances osteogenic differentiation through phosphorylation of Osterix

被引：21

作者：

Choi, You Hee ^{[1
,2
]}

Han, YounHo ^{[1
,2
]}

Lee, Sung Ho ^{[1
,2
]}

Cheong, Heesun ^{[5
]}

Chun, Kwang-Hoon ^{[6
]}

Yeo, Chang-Yeol ^{[3
,4
]}

Lee, Kwang Youl ^{[1
,2
]}

机构：

[1] Chonnam Natl Univ, Coll Pharm, Gwangju 500757, South Korea

[2] Chonnam Natl Univ, Res Inst Drug Dev, Gwangju 500757, South Korea

[3] Ewha Womans Univ, Dept Life Sci, Seoul 120750, South Korea

[4] Ewha Womans Univ, Div Life & Pharmaceut Sci, Seoul 120750, South Korea

[5] Natl Canc Ctr, Res Inst, Goyang Si 410769, Gyeonggi Do, South Korea

[6] Gachon Univ, Coll Pharm, Gachon Inst Pharmaceut Sci, Inchon 406799, South Korea

来源：

MOLECULAR AND CELLULAR ENDOCRINOLOGY | 2015年 / 407卷 / 0C期

基金：

新加坡国家研究基金会;

关键词：

Src; Osterix; Phosphorylation; Osteoblast; Differentiation; PROTEIN-TYROSINE-PHOSPHATASE; TRANSCRIPTION FACTOR OSTERIX; BONE MORPHOGENETIC PROTEINS; OSTEOBLAST DIFFERENTIATION; C-CBL; TARGETED DISRUPTION; NEGATIVE REGULATION; SIGNALING PATHWAY; MOLECULAR-BIOLOGY; PROLIFERATION;

D O I：

10.1016/j.mce.2015.03.010

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Osterix, a zinc-finger transcription factor, is required for osteoblast differentiation and new bone formation during embryonic development. The c-Src of tyrosine kinase is involved in a variety of cellular signaling pathways, leading to the induction of DNA synthesis, cell proliferation, and cytoskeletal reorganization. Src activity is tightly regulated and its dysregulation leads to constitutive activation and cellular transformation. The function of Osterix can be also modulated by post-translational modification. But the precise molecular signaling mechanisms between Osterix and c-Src are not known. In this study we investigated the potential regulation of Osterix function by c-Src in osteoblast differentiation. We found that c-Src activation increases protein stability, osteogenic activity and transcriptional activity of Osterix. The siRNA-mediated knockdown of c-Src decreased the protein levels and transcriptional activity of Osterix. Conversely, Src specific inhibitor, SU6656, decreased the protein levels and transcriptional activity of Osterix. The c-Src interacts with and phosphorylates Osterix These results suggest that c-Src signaling modulates osteoblast differentiation at least in part through Osterix. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

引用

页码：85 / 97

页数：13

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