Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Outline of Final Research Achievements |
Serine-threonine kinase 38 (STK38) is a member of the protein kinase A (PKA)/PKG/PKC-family and is implicated in the regulation of cell division and cell morphogenesis. Here, we show treatment with heat induced degradation of STK38. The calpain inhibitor calpeptin suppressed heat-induced STK38 cleavage. Moreover, in vitro cleavage assay demonstrate that calpain I directly cleaves STK38 at the proximal N-terminal region. Deletion of the N-terminus region increases its stability against heat. We further demonstrate that a MAPKK kinase (MAP3K), MEKK2 prevents heat-induced cleavage of STK38. MEKK2 knockdown enhanced heat-induced degradation of STK38. We performed in vitro MEKK2 assay and identified a key regulatory phosphorylation site in STK38 by MEKK2. Experiments with phosphorylation-defective mutant demonstrate that phosphorylation of Ser 91 is important for STK38 stability, as it is susceptible to attack by the calpain degradation pathway unless this residue is phosphorylated.
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