title: Involvement of STAP-2 in Brk-mediated phosphorylation and activation of STAT5 in breast cancer cells.
abstract: 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.
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ikeda
authors.forename: Akihiro
authors.initials: A
authors.lastname: Mizushima
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sekine
authors.forename: Chikako
authors.initials: C
authors.lastname: Yamamoto
authors.forename: Ryuta
authors.initials: R
authors.lastname: Muromoto
authors.forename: Asuka
authors.initials: A
authors.lastname: Nanbo
authors.forename: Kenji
authors.initials: K
authors.lastname: Oritani
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsuda
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; C413897:STAP2 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C088375:PTK6 protein, human