| Title: | Interactions of STAP-2 with Brk and STAT3 participate in cell growth of human breast cancer cells. |
| Authors: | Ikeda, Osamu Browse this author |
| Sekine, Yuichi Browse this author |
| Mizushima, Akihiko Browse this author |
| Nakasuji, Misa Browse this author |
| Miyasaka, Yuto Browse this author |
| Yamamoto, Chikako Browse this author |
| Muromoto, Ryuta Browse this author →KAKEN DB |
| Nanbo, Asuka Browse this author →KAKEN DB |
| Oritani, Kenji Browse this author |
| Yoshimura, Akihiko Browse this author |
| Matsuda, Tadashi Browse this author |
| Keywords: | Adaptor proteins |
| Breast cancer |
| Protein phosphorylation |
| Signal transduction |
| Transcription factors |
| Tyrosine protein kinase (Tyrosine kinase) |
| Brk |
| STAP-2 |
| STAT3 |
| Issue Date: | 6-Dec-2010 |
| Journal Title: | The Journal of Biological Chemistry |
| Volume: | 285 |
| Issue: | 49 |
| Start Page: | 38093 |
| End Page: | 38103 |
| Publisher DOI: | 10.1074/jbc.M110.162388 |
| Abstract: | Signal transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein, which contains pleckstrin homology (PH) and Src homology 2 (SH2)-like domains, as well as a signal transducer and an activator of transcription 3 (STAT3)-binding motif in its C-terminal region. STAP-2 is also a substrate of breast tumor kinase (Brk). In breast cancers, Brk expression is deregulated and it promotes STAT3-dependent cell proliferation. In the present study, manipulated STAP-2 expression demonstrated essential roles of STAP-2 in Brk-mediated STAT3 activation. STAP-2 interacts with both Brk and STAT3. In addition, small-interfering RNA-mediated reduction of endogenous STAP-2 expression strongly decreased Brk-mediated STAT3 activation in T47D breast cancer cells. The PH domain of STAP-2 is involved in multiple steps; the binding between Brk and STAP-2, the activation and tyrosine phosphorylation of STAT3, and the activation of Brk. Notably, a STAP-2 PH-Brk fusion protein exhibited robust kinase activity and increased activation and tyrosine phosphorylation of STAT3. Finally, STAP-2-knockdown in T47D cells induced a significant decrease of proliferation, as strong as that of Brk- or STAT3-knockdown. Taken together, our findings are likely to inform the development of a novel therapeutic strategy, as well as the determination of novel prognostic values, in breast carcinomas. |
| Rights: | Copyright (c) [yyyy] the American Society for Biochemistry and Molecular Biology |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/44383 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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