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

Osamu Ikeda, Yuichi Sekine, Akihiro Mizushima, Misa Nakasuji, Yuto Miyasaka, Chikako Yamamoto, Ryuta Muromoto, Asuka Nanbo, Kenji Oritani, Akihiko Yoshimura, Tadashi Matsuda

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

STAP-2 (signal transducing adaptor protein-2) is a recently identified adaptor protein that contains pleckstrin homology (PH) and Src homology 2-like domains, as well as a 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 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.

Original languageEnglish
Pages (from-to)38093-38103
Number of pages11
JournalJournal of Biological Chemistry
Volume285
Issue number49
DOIs
Publication statusPublished - 2010 Dec 3

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Signal Transducing Adaptor Proteins
Cell growth
Tumors
Phosphotransferases
Cells
Breast Neoplasms
Growth
Chemical activation
Phosphorylation
Tyrosine
Cell proliferation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Ikeda, O., Sekine, Y., Mizushima, A., Nakasuji, M., Miyasaka, Y., Yamamoto, C., ... Matsuda, T. (2010). Interactions of STAP-2 with Brk and STAT3 participate in cell growth of human breast cancer cells. Journal of Biological Chemistry, 285(49), 38093-38103. https://doi.org/10.1074/jbc.M110.162388

Interactions of STAP-2 with Brk and STAT3 participate in cell growth of human breast cancer cells. / Ikeda, Osamu; Sekine, Yuichi; Mizushima, Akihiro; Nakasuji, Misa; Miyasaka, Yuto; Yamamoto, Chikako; Muromoto, Ryuta; Nanbo, Asuka; Oritani, Kenji; Yoshimura, Akihiko; Matsuda, Tadashi.

In: Journal of Biological Chemistry, Vol. 285, No. 49, 03.12.2010, p. 38093-38103.

Research output: Contribution to journalArticle

Ikeda, O, Sekine, Y, Mizushima, A, Nakasuji, M, Miyasaka, Y, Yamamoto, C, Muromoto, R, Nanbo, A, Oritani, K, Yoshimura, A & Matsuda, T 2010, 'Interactions of STAP-2 with Brk and STAT3 participate in cell growth of human breast cancer cells', Journal of Biological Chemistry, vol. 285, no. 49, pp. 38093-38103. https://doi.org/10.1074/jbc.M110.162388
Ikeda, Osamu ; Sekine, Yuichi ; Mizushima, Akihiro ; Nakasuji, Misa ; Miyasaka, Yuto ; Yamamoto, Chikako ; Muromoto, Ryuta ; Nanbo, Asuka ; Oritani, Kenji ; Yoshimura, Akihiko ; Matsuda, Tadashi. / Interactions of STAP-2 with Brk and STAT3 participate in cell growth of human breast cancer cells. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 49. pp. 38093-38103.
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