2006 Fiscal Year Final Research Report Summary
Regulatory Mechanism of Stress-Responsive Signal Transduction Pathway in Human and Yeast Cells
| Project/Area Number |
14086202
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
|
| Allocation Type | Single-year Grants |
|---|
| Review Section |
Biological Sciences
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
SAITO Haruo The University of Tokyo, Institute of Medical Science, Professor (60114485)
|
|---|
| Project Period (FY) |
2002 – 2006
|
| Keywords | gene / environment / enzyme / signal transduction / stress |
|---|
| Research Abstract |
1) Regulatory mechanism of human stress-responsive signal transduction pathway
We revealed the mechanism of MTK1 activation by the stress-inducible Gadd45 proteins. Gadd45 binds to the N-terminal region of the MTK1, induces an N-C dissociation in MTK1 molecule, and thus facilitates MTK1 dimerization that leads to MTK1 activation by auto-phosphorylation. We showed that TGF-beta activates MTK1 through induction of the expression of Gadd45. We also identified a novel docking interaction between stress-activated MAPKKK (SAP3K) and stress-activated MAPKK (SAP2K). We showed that a C-terminal region in SAP2K, termed the DVD domain, was essential for this interaction, and elucidated its role in SAP2K activation. Using the specific interaction through DVD domain, we developed a new FRET probe to visualize SAP3K activity in single living cells.
2) Regulatory mechanism of yeast stress-responsive signal transduction pathway.
We identified the mucin-like membrane glycoproteins Hkr1 and Msb2 as putative osmosensors in the Sho1 branch of Hog1 MAPK pathway. We found a specific docking interaction between yeast osmoregulatory Ssk2 SAP3K and Pbs2 SAP2K, and showed that the interaction is essential for specific activation of Pbs2 by Ssk2. We also analyzed the functional roles of the docking interaction between Hog 1 and its activator, the Pbs2 SAP2K, as well as that between Hog1 and its inactivator, the Ptp2 protein tyrosine phosphatase. Finally, we found that the membrane protein Sho1, the cytoplasmic protein Ste50, and the small G-protein Cdc42 serve as adaptor proteins in yeast osmoregulatory Hog1 MAPK pathway.
|
-
-
-
[Journal Article] Transmembrane mucinsHkr1andMsb2areputativeosmosensorsinthe SHO1 branch of yeast HOG pathway.2007
Author(s)
Tatebayashi, K., Tanaka, K., Yang, H. -Y., Yamamoto, K., Matsushita, Y., Tomida, T., Imai, M., Saito, H.
-
Journal Title
EMBO J. 26
Pages: 3521-3533
Description
「研究成果報告書概要(欧文)」より
-
-
-
[Journal Article] Adaptor functions of Cdc42, Ste50, and Sho1 in the yeast osmoregulatory HOG MAPK pathway.2006
Author(s)
Tatebayashi, K., Yamamoto, K., Tanaka, K., Tomida, T., Maruoka, T., Kasukawa, E., Saito, H.
-
Journal Title
EMBO J. 25
Pages: 3033-3044
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] Functions of the ectodomain and cytoplasmic tyrosine phosphatase domains of receptor protein tyrosine phosphatase Dlarinvivo.2003
Author(s)
Krueger, N. X., Reddy, R. S., Johnson, K., Bateman, J., Kaufmann, N., Scalice, D., Van Vactor, D., Saito, H.
-
Journal Title
Mol. Cell. Biol. 23
Pages: 6909-6921
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
-
-
-
[Journal Article] Smad-dependent GADD45b expression mediates delayed activation of p38 MAP kinase by TGF-b.2002
Author(s)
Takekawa, M., Tatebayashi, K., Itoh, F., Adachi, M., Imai, K., Saito, H.
-
Journal Title
EMBO J. 21
Pages: 6473-6482
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Regulation of Lck and Fyn tyrosine kinase activities by transmembrane protein tyrosine phosphatase leukocyte common antigen-related molecule.2002
Author(s)
Tsujikawa, K., Ichijo, T., Moriyama, K., Tadotsu, N., Sakamoto, K., Sakane, N., Fukada, S., Furukawa, T., Saito, H., Yamamoto, H.
-
Journal Title
Mol. Cancer Res. 1
Pages: 155-163
Description
「研究成果報告書概要(欧文)」より
