A5086206547- Biochemical and Molecular Research
- Protein Kinase Regulation and GTPase Signaling
- Cytokine Signaling Pathways and Interactions
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- PI3K/AKT/mTOR signaling in cancer
- Cellular Mechanics and Interactions
- Cellular transport and secretion
- Metabolism, Diabetes, and Cancer
- Prostate Cancer Treatment and Research
- HIV/AIDS drug development and treatment
- Medicinal Plant Pharmacodynamics Research
- Epigenetics and DNA Methylation
- Cancer-related Molecular Pathways
- interferon and immune responses
- PARP inhibition in cancer therapy
- Fibroblast Growth Factor Research
- Glioma Diagnosis and Treatment
- Signaling Pathways in Disease
- Amino Acid Enzymes and Metabolism
- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- Protein Tyrosine Phosphatases
- Adenosine and Purinergic Signaling
- Ubiquitin and proteasome pathways
Keio University
2019-2025
University of Cincinnati Medical Center
2015-2025
Hiroshima University Hospital
2023-2025
Tokyo Medical and Dental University
2024
University of Cincinnati
2013-2022
Allen Institute for Brain Science
2019-2021
Cancer Institute (WIA)
2016-2019
Oncology Hematology Care
2016
Harvard University
2006-2013
Center for Systems Biology
2008-2013
Numerous studies have established a causal link between aberrant mammalian target of rapamycin (mTOR) activation and tumorigenesis, indicating that mTOR inhibition may therapeutic potential. In this study, we show its analogs activate the MAPK pathway in human cancer, what represents novel mTORC1-MAPK feedback loop. We found tumor samples from patients with biopsy-accessible solid tumors advanced disease treated RAD001, derivative, showed an administration schedule–dependent increase...
Control of intracellular reactive oxygen species (ROS) concentrations is critical for cancer cell survival. We show that, in human lung cells, acute increases ROS caused inhibition the glycolytic enzyme pyruvate kinase M2 (PKM2) through oxidation Cys(358). This PKM2 required to divert glucose flux into pentose phosphate pathway and thereby generate sufficient reducing potential detoxification ROS. Lung cells which endogenous was replaced with Cys(358) Ser(358) oxidation-resistant mutant...
During chemotaxis, receptors and heterotrimeric G-protein subunits are distributed activated almost uniformly along the cell membrane, whereas PI(3,4,5)P3, product of phosphatidylinositol 3-kinase (PI3K), accumulates locally at leading edge. The key intermediate event that creates this strong PI(3,4,5)P3 asymmetry remains unclear. Here, we show Ras is rapidly transiently in response to chemoattractant stimulation regulates PI3K activity. activation occurs edge chemotaxing cells, local...
Background The Janus family of protein tyrosine kinases (JAKs) regulate cellular processes involved in cell growth, differentiation and transformation through their association with cytokine receptors. We have recently identified the JAK‐binding protein, JAB that inhibits various cytokine‐dependent JAK signalling pathways. JAK2 kinase activity by binding to domain (JH1 domain) N‐terminal inhibitory region (KIR) SH2 domain. has been shown bind phosphorylated Y1007 activation loop JH1. also...
The cytokine-inducible SH2 protein-3 (CIS3/SOCS-3/SSI-3) has been shown to inhibit the JAK/STAT pathway and act as a negative regulator of fetal liver erythropoiesis. Here, we studied molecular mechanisms by which CIS3 regulates erythropoietin (EPO) receptor (EPOR) signaling in erythroid progenitors Ba/F3 cells expressing EPOR (BF-ER). binds directly well JAK2 inhibits EPO-dependent proliferation STAT5 activation. We have identified region containing Tyr(401) cytoplasmic domain direct...
Interleukin-6 (IL-6) activates the Jak/STAT pathway as well mitogen-activated protein kinase cascade. Tyrosine 759 of IL-6 signal-transducing receptor subunit gp130 has been identified being involved in negative regulation IL-6-induced gene induction and activation pathway. Because this site is known to be a recruitment motif for protein-tyrosine phosphatase SHP2, it suggested that SHP2 mediator tyrosine 759-dependent signal attenuation. We recently observed suppressor cytokine-signaling...
Phosphoinositide 3-kinase (PI3K)γ and Dictyostelium PI3K are activated via G protein–coupled receptors through binding to the Gβγ subunit Ras. However, mechanistic role(s) of Ras in activation remains elusive. Furthermore, dynamics function absence extracellular stimuli have not been fully investigated. We report that gβ null cells display activation, as well reciprocal localization PTEN, which lead local accumulation PI(3,4,5)P3. Simultaneous imaging analysis reveals stimuli, autonomous...
Dictyostelium cells form a multicellular organism through the aggregation of independent cells. This process requires both chemotaxis and signal relay in which chemoattractant cAMP activates adenylyl cyclase G protein-coupled receptor cAR1. is produced secreted it receptors on neighboring cells, thereby relaying to distant Using coimmunoprecipitation mass spectrometric analyses, we have identified TOR-containing complex that related TORC2 Saccharomyces cerevisiae regulates relay. We...
Cancers in which K-Ras activation drives tumor growth could be targeted by treatments blocking ubiquitination.
ATP citrate lyase (ACL) catalyzes the conversion of cytosolic to acetyl-CoA and oxaloacetate. A definitive role for ACL in tumorigenesis has emerged from RNAi chemical inhibitor studies, showing that inhibition limits tumor cell proliferation survival induces differentiation vitro. In vivo, it reduces growth leading a cytostatic effect differentiation. However, underlying molecular mechanisms are poorly understood agents could enhance efficacy have not been identified. Our studies focus on...
Stress granules (SGs) are large cytoplasmic ribonucleoprotein complexes that assembled when cells exposed to stress. SGs promote the survival of stressed by contributing reprogramming protein expression as well blocking pro-apoptotic signaling cascades. These cytoprotective effects implicated in resistance cancer radiation and chemotherapy. We have found sodium selenite, a selenium compound with chemotherapeutic potential, is potent inducer SG assembly. Selenite-induced differ from canonical...
Various mitogenic stimuli such as epidermal growth factor (EGF), fibroblast (FGF), and phorbol 12,13-dibutyrate (PDBu) activate the Ras-Raf-MEK-ERK pathway, but regulatory mechanism of this pathway remains to be investigated. Here we found that in 293 cells, mammalian Sprouty2 Sprouty4 were rapidly induced by EGF, FGF, PDBu an ERK pathway-dependent manner. Forced expression inhibited FGF-induced activation did not affect EGF- or PDBu-induced activation. To examine whether endogenous Sproutys...