Regulatory mechanisms of the environmental stress-responsive MAP kinase signal pathway

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1) Functional roles and regulation of human stress-activated MAP kinase signal transduction pathway.We identified a novel docking interaction between stress-activated MAPKKK (SAP3K) and stress-activated MAPKK (SAP2K). We also found that a C-terminal region in SAP2K, termed the DVD domain, is 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. Furthermore, we revealed the mechanism of MTK1 activation by the stress-inducible Gadd45 proteins. Gadd45 binds to the N-terminal region of MTK1 SAP3K, induces an N-C dissociation in. MTK1 molecule, and thus facilitates MTK1 dimerization that leads to MTK1 activation by auto-phosphorylation.2) Functional roles and regulation of yeast stress-activated MAP kinase signal transduction pathway.We identified a specific docking interaction between yeast osmoregulatory Ssk2 SAP3K and Pbs2 SAP2K, and revealed that the interaction is essential for specific activation of Pbs2 by Ssk2. We found that the membrane protein Sho1, the cytoplasmic protein Ste50, and the small G-protein Cdc42 bind, serve as adaptor proteins in yeast osmoregulatory Hog1 MAPK pathway. We also revealed that the mucin-like membrane glycoproteins Hkr1 and Msb2 are putative osmosensors in the Sho1 branch of Hog1 MAPK pathway. We proposed that external osmostress causes a conformation change in the mucin domains of Hkrl/Msb2, and thus induces an interaction between Sho1 and Hkrl/Msb2 to activate the Hog1 MAPK pathway.