HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Faculty of Pharmaceutical Sciences >
Peer-reviewed Journal Articles, etc >

Interactions of STAP-2 with Brk and STAT3 participate in cell growth of human breast cancer cells.

Files in This Item:
JBC-revised.pdf3.92 MBPDFView/Open
Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/44383

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)

Submitter: 松田 正

Export metadata:

OAI-PMH ( junii2 , jpcoar )

MathJax is now OFF:


 

Feedback - Hokkaido University