| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
The phosphrylated amino acid residues in animal cells studied most to date are Ser, Thr, and Tyr, all of which form acid-stable ester linkages with phosphate. We recently, however, found protein-histidyl phosphorylation activities in rat liverextract during studying the mode of action of the peroxisome proliferators.
To investigate the physiological roles of the protein histidyl phosphorylation and their involvement in the primary action of the peroxisome proliferators to cause the transcriptional activation, we serached for the specific inhibitors against the kinase.
Among the popular protein kinase inhibitors, only staurosporine inhibited the histidine kinase at almost the same low concentrations as for protein kinase C.New inhibitors were also screened among the recently synthesized new organic compounds in our school and the cultured media with dozens of Streptomyces strains. These screenings, however, uncovered no compound to specifically inhibit the kinase. It will be necessary to screen much larger number of compounds using more efficient method.
Along with these screening studies, we identified the kinases, that are activated during the early phase of the peroxisome proliferator action, as protein kinase C and the histidine kinase. As mentioned above, these two kinases are inhibited by low concentrations of staurosporine, and their roles in the proliferator action can be studied using this inhibitor. As a result we concluded that protein kinase C and the histidine kinase are activated during the early phase of the proliferator action but the activation is not required for the action to induce transcriptional activation of several peroxisomal genes.
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