RESEARCH

1)   TOR (Target Of Rapamycin) signal pathway

The TOR protein kinase was originally identified as a cellular target of the antibiotic rapamycin, a potent  immunosuppressant drug. TOR kinase forms a protein complex called TORC2 (TOR complex2), which mediates insulin-induced activation of the Akt protein kinase (also known as Protein kinase B, PKB) and cellular uptake of glucose. Defects in insulin signaling result in type 2 diabetes and therefore, comprehensive understanding of this pathway is critical to develop informed strategies to treat the disease. We have established a model system in S. pombe to discover molecular mechanisms that control TORC2 activity.

 

References :

 

Morigasaki, S., Chin, L.C., Hatano, T., Emori, M., Iwamoto, M., Tatebe, H., and Shiozaki, K. (2019). Modulation of TOR complex 2 signaling by the stress-activated MAPK pathway in fission yeast. J Cell Sci

 

Tatebe, H., and Shiozaki, K. (2017). Evolutionary Conservation of the Components in the TOR Signaling Pathways. Biomolecules 7, E77.

 

Tatebe, H., Murayama, S., Yonekura, T., Hatano, T., Richter, D., Furuya, T., ... & Shiozaki, K. (2017). Substrate specificity of TOR complex 2 is determined by a ubiquitin-fold domain of the Sin1 subunit. eLife, 6, e19594.

 

Hatano, T., Morigasaki, S., Tatebe, H., Ikeda, K., and Shiozaki, K. (2015). Fission yeast Ryh1 GTPase activates TOR Complex 2 in response to glucose. Cell Cycle 14, 848-856

 

Tatebe, H., Morigasaki, S., Murayama, S., Zeng, C.T. and Shiozaki, K. (2010). Rab-family GTPase regulates TOR complex 2 signaling in fission yeast. Curr. Biol. 20, 1975-1982.

 

Ikeda, K., Morigasaki, S., Tatebe, H., Tamanoi, F. and Shiozaki, K. (2008). Fission yeast TOR complex 2 activates the AGC-family Gad8 kinase essential for stress resistance and cell cycle control. Cell Cycle 7, 358-364.

 

 

 

 

2) Stress-responsive MAP kinase cascade

 

Unicellular organisms as well as cells in higher organisms have mechanisms to sense and adopt to a variety of stress, significant fluctuations in the environmental conditions. Stress-activated protein kinase (SAPK) is a member of the MAP kinase family that plays pivotal roles in cellular stress responses, including those of cancer cells exposed to cytotoxic therapies. Our goal is to discover cellular stress sensor that transmit signals to induce activation of SAPK.

 

References :

Morigasaki, S., Chin, L.C., Hatano, T., Emori, M., Iwamoto, M., Tatebe, H., and Shiozaki, K. (2019). Modulation of TOR complex 2 signaling by the stress-activated MAPK pathway in fission yeast. J Cell Sci

 

Morigasaki S, Ikner A, Tatebe H, Shiozaki K.(2013). Response regulator-mediated MAPKKK heteromer promotes stress signaling to the Spc1 MAPK in fission yeast. Mol. Biol. Cell. 23, 1083-92. 

 

Morigasaki, S., Shimada, K., Ikner, A., Yanagida, M. and Shiozaki, K. (2008). Glycolytic enzyme GAPDH promotes peroxide stress signaling through multistep phosphorelay to a MAPK cascade. Mol. Cell 30, 108-113.

 

Wang, L., Shimada, K. Morishita, M. and Shiozaki, K. (2005). Response of fission yeast to toxic cations involves cooperative action of the stress-activated protein kinase Spc1/Sty1 and the Hal4 protein kinase. Mol. Cell. Biol. 25, 3945-3955.

 

Tatebe, H., and Shiozaki, K. (2003). Identification of Cdc37 as a novel regulator of the stress-responsive mitogen-activated protein kinase. Mol Cell Biol 23, 5132-142.

 

Nguyen, A. N., Ikner, A., Shiozaki, M., Warren, S. and Shiozaki, K. (2002). Cytoplasmic localization of Wis1 MAPKKK by nuclear export signal is important for nuclear targeting of Spc1/Sty1 MAPK in fission yeast. Mol. Biol. Cell 13, 2651-2663.

 

Nguyen, A. N., Lee, A., Place, W. and Shiozaki, K. (2000). Multistep phosphorelay proteins transmit oxidative stress signals to the fission yeast stress-activated protein kinase. Mol. Biol. Cell 11, 1169-1181.