title: Src enhances osteogenic differentiation through phosphorylation of Osterix.
abstract: 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.
authors: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, South Korea.
authors: You Hee
authors: YH
authors: Choi
authors: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, South Korea.
authors: YounHo
authors: Y
authors: Han
authors: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, South Korea.
authors: Sung Ho
authors: SH
authors: Lee
authors: Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-769, South Korea.
authors: Heesun
authors: H
authors: Cheong
authors: Gachon Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, Incheon 406-799, South Korea.
authors: Kwang-Hoon
authors: KH
authors: Chun
authors: Department of Life Science and Division of Life & Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, South Korea.
authors: Chang-Yeol
authors: CY
authors: Yeo
authors: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, South Korea. Electronic address: kwanglee@chonnam.ac.kr.
authors: Kwang Youl
authors: KY
authors: Lee
mesh_terms: D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D055550:Protein Stability; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000076182:Sp7 Transcription Factor; D013449:Sulfonamides / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; C416927:SU 6656; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D013449:Sulfonamides; D014157:Transcription Factors; D004247:DNA; D008156:Luciferases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human
keywords: Differentiation; Osteoblast; Osterix; Phosphorylation; Src