Publications by authors named "H Tokumitsu"
Article Synopsis
- A chemical proteomics study using TIM-063-Kinobeads identified primary targets like CaMKKα/1 and β/2, and also highlighted potential off-target kinases such as AAK1.
- The study found a new, more potent AAK1 inhibitor, TIM-098a, which has a significantly lower IC value of 0.24 µM and selectively inhibits AAK1 without affecting CaMKK isoforms.
- TIM-098a was shown to inhibit AAK1 activity in living cells and blocked the reduction of early endosomes in HeLa cells, suggesting its potential as a selective and therapeutically valuable AAK1 inhibitor.
Article Synopsis
- Raf-1 is a multifunctional kinase that regulates important cellular processes, and its activity is controlled by various mechanisms, including interactions with regulatory proteins and phosphorylation.
- The study demonstrates that PHI-1, an inhibitor of protein phosphatase-1 (PP1), is crucial for maintaining Raf-1 levels in cells; knocking down PHI-1 leads to increased cell proliferation and reduced apoptosis by enhancing Raf-1 expression and ERK1/2 phosphorylation.
- Ectopic expression of PHI-1 lowers Raf-1 levels, and inhibiting PP1 mimics PHI-1's effects, indicating that the PHI-1-PP1 axis plays a key role in regulating Raf-1 stability and survival
Ca/calmodulin-dependent protein kinase kinase (CaMKK) phosphorylates and activates downstream protein kinases, including CaMKI, CaMKIV, PKB/Akt, and AMPK; thus, regulates various Ca-dependent physiological and pathophysiological pathways. Further, CaMKKβ/2 in mammalian species comprises multiple alternatively spliced variants; however, their functional differences or redundancy remain unclear. In this study, we aimed to characterize mouse CaMKKβ/2 splice variants (CaMKKβ-3 and β-3x).
View Article and Find Full Text PDFCalmodulin (CaM) is known to function as a central signal transducer in calcium-mediated intracellular pathways. In this study, a fusion molecule of a recently developed proximity biotinylation enzyme (AirID) with rat CaM (AirID-CaM) was expressed and purified to near homogeneity using an E. coli expression system to examine the physical interactions between CaM and its target proteins by converting the interaction to biotinylation of CaM targets under nondenatured conditions.
View Article and Find Full Text PDFCa/calmodulin-dependent protein kinase kinase (CaMKK) is the activating kinase for multiple downstream kinases, including CaM-kinase I (CaMKI), CaM-kinase IV (CaMKIV), protein kinase B (PKB/Akt), and 5'AMP-kinase (AMPK), through the phosphorylation of their activation-loop Thr residues in response to increasing the intracellular Ca concentration, as CaMKK itself is a Ca/CaM-dependent enzyme. The CaMKK-mediated kinase cascade plays important roles in a number of Ca-dependent pathways, such as neuronal morphogenesis and plasticity, transcriptional activation, autophagy, and metabolic regulation, as well as in pathophysiological pathways, including cancer progression, metabolic syndrome, and mental disorders. This review focuses on the molecular mechanism underlying CaMKK-mediated signal transduction in normal and pathophysiological conditions.
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