Interactions of STAP-2 with Brk and STAT3 Participate in Cell Growth of Human Breast Cancer Cells
| Autor: | Yuichi Sekine, Misa Nakasuji, Osamu Ikeda, Asuka Nanbo, Tadashi Matsuda, Akihiro Mizushima, Kenji Oritani, Yuto Miyasaka, Akihiko Yoshimura, Chikako Yamamoto, Ryuta Muromoto |
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| Rok vydání: | 2010 |
| Předmět: |
STAT3 Transcription Factor
Tyrosine protein kinase (Tyrosine kinase) Amino Acid Motifs Breast Neoplasms STAP-2 Signal transduction Biology Biochemistry STAT3 chemistry.chemical_compound Breast cancer Protein phosphorylation Adaptor proteins Transcription factors Humans Phosphorylation RNA Small Interfering Kinase activity Molecular Biology Adaptor Proteins Signal Transducing Signal transducing adaptor protein Tyrosine phosphorylation Cell Biology Protein-Tyrosine Kinases Phosphoproteins Neoplasm Proteins Gene Expression Regulation Neoplastic Pleckstrin homology domain chemistry Brk Cancer research Female HeLa Cells Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Journal of Biological Chemistry. 285:38093-38103 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m110.162388 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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