Involvement of STAP-2 in Brk-mediated phosphorylation and activation of STAT5 in breast cancer cells
Osamu Ikeda
Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo
These authors contributed equally to this work.
Search for more papers by this authorAkihiro Mizushima
Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo
These authors contributed equally to this work.
Search for more papers by this authorYuichi Sekine
Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo
Search for more papers by this authorChikako Yamamoto
Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo
Search for more papers by this authorRyuta Muromoto
Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo
Search for more papers by this authorAsuka Nanbo
Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo
Search for more papers by this authorKenji Oritani
Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, Osaka
Search for more papers by this authorAkihiko Yoshimura
Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Tadashi Matsuda
Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo
To whom correspondence should be addressed.E-mail: [email protected]Search for more papers by this authorOsamu Ikeda
Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo
These authors contributed equally to this work.
Search for more papers by this authorAkihiro Mizushima
Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo
These authors contributed equally to this work.
Search for more papers by this authorYuichi Sekine
Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo
Search for more papers by this authorChikako Yamamoto
Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo
Search for more papers by this authorRyuta Muromoto
Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo
Search for more papers by this authorAsuka Nanbo
Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo
Search for more papers by this authorKenji Oritani
Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, Osaka
Search for more papers by this authorAkihiko Yoshimura
Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Tadashi Matsuda
Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo
To whom correspondence should be addressed.E-mail: [email protected]Search for more papers by this authorAbstract
Signal-transducing adaptor protein (STAP)-2 is a recently identified adaptor protein that contains Pleckstrin homology and Src homology 2-like domains, and is also known to be a substrate of breast tumor kinase (Brk). In a previous study, we found that STAP-2 upregulated Brk-mediated activation of signal transducer and activator of transcription (STAT) 3 in breast cancer cells. Here, we examined the involvement of STAP-2 in Brk-mediated STAT5 activation in breast cancer cells. Ectopic expression of STAP-2 induced Brk-mediated transcriptional activity of STAT5. Furthermore, STAP-2-knockdown in T47D breast cancer cells induced a marked decrease in proliferation that was as strong as that after Brk- or STAT5b-knockdown. Regarding the mechanism, the Pleckstrin homology domain of STAP-2 is likely to participate in the process by which Brk phosphorylates and activates STAT5. Taken together, our findings provide insights toward the development of novel therapeutic strategies as well as novel prognostic values in breast carcinomas. (Cancer Sci 2011; 102: 756–761)
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