Molecular mechanism analysis of STAT activation in breast tumor cells regulated by adaptor protein

Research Project

Project/Area Number	26440016
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Structural biochemistry
Research Institution	Hokkaido University
Principal Investigator	OSE Toyoyuki 北海道大学, 薬学研究院, 准教授 (80380525)
Project Period (FY)	2014-04-01 – 2017-03-31
Project Status	Completed (Fiscal Year 2016)
Budget Amount *help	¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000) Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywords	蛋白質 / 蛋白質構造 / シグナル伝達
Outline of Final Research Achievements	The non-receptor tyrosine kinase breast tumor kinase (Brk), has been identified as a highly expressed Protein-tyrosine kinases in human melanocyte. Brk was reported to play key roles for cancer progression via overactivation of Signal Transducers and Activator of Transcription (STAT), especially STAT3 and STAT5. This activation is mediated by an adaptor protein STAP-2, which expresses ubiquitously and harobors many important functions for cell signal regulation. We successfully expressed recombinant Brk and STAP-2 including their mutants, checked kinase activity, monitored interactions, and structurally analyzed using small angle x-ray scattering (SAXS). The C-terminal phosphorylation site of Brk is, on the contrary to our expectation, didn’t produce open/close conformational change.