A5022645715- Cancer Cells and Metastasis
- Protein Kinase Regulation and GTPase Signaling
- Wnt/β-catenin signaling in development and cancer
- PI3K/AKT/mTOR signaling in cancer
- Metabolism, Diabetes, and Cancer
- Hippo pathway signaling and YAP/TAZ
- Cancer Genomics and Diagnostics
- Pancreatic function and diabetes
- Cancer-related Molecular Pathways
- TGF-β signaling in diseases
- Liver physiology and pathology
- Epigenetics and DNA Methylation
- Breast Cancer Treatment Studies
- Melanoma and MAPK Pathways
- Estrogen and related hormone effects
- Cancer, Hypoxia, and Metabolism
- Barrier Structure and Function Studies
- Genetics, Aging, and Longevity in Model Organisms
- RNA modifications and cancer
- Genetic factors in colorectal cancer
- Immune Cell Function and Interaction
- NF-κB Signaling Pathways
- Axon Guidance and Neuronal Signaling
- Connexins and lens biology
- Gastric Cancer Management and Outcomes
Tokyo University of Science
2015-2024
Yokohama City University
2008-2018
Tokyo Women's Medical University Hospital
2015-2018
Kanagawa Cancer Center
2018
Kanagawa Prefectural Hospital Organization
2018
Molecular Biology Consortium
2009
Tokyo Metropolitan Institute of Medical Science
1991
We have previously shown that during early Caenorhabditis elegans embryogenesis PKC-3, a C. atypical PKC (aPKC), plays critical roles in the establishment of cell polarity required for subsequent asymmetric cleavage by interacting with PAR-3 [Tabuse, Y., Y. Izumi, F. Piano, K.J. Kemphues, J. Miwa, and S. Ohno. 1998. Development (Camb.). 125:3607–3614]. Together fact aPKC mammalian homologue, aPKC-specific protein (ASIP), colocalize at tight junctions polarized epithelial cells (Izumi, H....
Phosphoinositide (PI) 3-kinase contributes to a wide variety of biological actions, including insulin stimulation glucose transport in adipocytes. Both Akt (protein kinase B), serine-threonine with pleckstrin homology domain, and atypical isoforms protein C (PKCzeta PKClambda) have been implicated as downstream effectors PI 3-kinase. Endogenous or transfected PKClambda 3T3-L1 adipocytes CHO cells has now shown be activated by manner sensitive inhibitors (wortmannin dominant negative mutant...
Protein kinase C (PKC)-related cDNA clones isolated from libraries of mouse P19 embryonal carcinoma cells and brain encoded a 67-kDa protein, PKC lambda. lambda shows the highest amino acid sequence identity with zeta (72%), third class family. Northern blot analysis showed that mRNA for is expressed in wide variety tissues, including NIH 3T3 cells, as well brain, kidney, testis, ovary. In undifferentiated most abundant among all family members. The differentiation results an increase alpha...
In developing mammalian telencephalon, the loss of adherens junctions and cell cycle exit represent crucial steps in differentiation neuroepithelial cells into neurons, but relationship between these cellular events remains obscure. Atypical protein kinase C (aPKC) is known to contribute junction formation epithelial fate determination for Drosophila neuroblasts. To elucidate functions aPKCλ, one out two aPKC members, mouse neocortical neurogenesis, a Nestin-Cre mediated conditional gene...
PKCλ is implicated as a downstream effector of PI3K in insulin action. We show here that mice lack specifically the liver (L-λKO mice), produced with use Cre-loxP system, exhibit increased sensitivity well decreased triglyceride content and reduced expression sterol regulatory element–binding protein-1c (SREBP-1c) gene liver. Induction hepatic Srebp1c its target genes involved fatty acid/triglyceride synthesis by fasting refeeding or an active form was inhibited L-λKO compared control...
Protein kinase C (PKC), a major cellular receptor for tumor-promoting phorbol esters and diacylglycerols (DGs), appears to be involved in variety of functions, although its activation mechanism vivo is not yet fully understood. To evaluate the signaling pathways PKC epsilon upon stimulation by platelet-derived growth factor (PDGF) (PDGFR), we used series PDGFR "add-back" mutants. Activation mutant (Y40/51) that binds activates phosphatidylinositol 3-kinase (PI 3-kinase) caused translocation...
PKCλ is implicated as a downstream effector of PI3K in insulin action. We show here that mice lack specifically the liver (L-λKO mice), produced with use Cre-loxP system, exhibit increased sensitivity well decreased triglyceride content and reduced expression sterol regulatory element–binding protein-1c (SREBP-1c) gene liver. Induction hepatic Srebp1c its target genes involved fatty acid/triglyceride synthesis by fasting refeeding or an active form was inhibited L-λKO compared control...
Epithelial cysts are one of the fundamental architectures for mammalian organogenesis. Although in vitro studies using cultured epithelial cells have revealed proteins required cyst formation, mechanisms that orchestrate functions these vivo remain to be clarified. We show targeted disruption mouse Par3 gene results midgestational embryonic lethality with defective epicardial development. The epicardium is mainly derived from and essential cardiomyocyte proliferation during cardiac...
Detection of anomalous cells such as cancer from normal blood has the potential to contribute greatly diagnosis and therapy. Conventional methods for detection are usually tedious cumbersome. Herein, we report on use a particle size analyzer convenient size-based differentiation cells. Measurements made using revealed that parameters significantly greater (e.g., inner diameter width) than corresponding values (white (WBC), lymphocytes splenocytes), with no significant difference in shape...
Understanding the mechanism by which hormone refractory prostate cancer (HRPC) develops remains a major issue. Alterations in HRPC include androgen receptor (AR) changes. In addition, AR is activated cytokines such as interleukin-6 (IL-6). Atypical protein kinase C (aPKClambda/iota) has been implicated progression of several cancers. Herein, we provide evidence that aPKClambda/iota expression correlates with recurrence. Experiments vitro and vivo revealed to be involved cell growth through...
IntroductionIn general, it has been considered that estrogen receptor-positive (ER+) breast cancer a good prognosis and is responsive to endocrine therapy. However, one third of patients with ER+ exhibit therapy resistance, many develop recurrence die 5 10 years after diagnosis. In cancer, major problem distinguish those most likely or metastatic disease within diagnosis from sufficiently prognosis.Materials MethodsWe downloaded the messenger RNA expression data clinical information for 401...
Rat fibroblast 3Y1 cells express at least three protein kinase C species, conventional PKC alpha (cPKC alpha), novel delta (nPKC delta), and epsilon epsilon). The stimulation of quiescent by serum (or epidermal growth factor (EGF) but not 12-O-tetradecanoylphorbol-13-acetate (TPA) results in the induction DNA synthesis. Upon or EGF, endogenous species showed no indication activation such as translocation down-regulation, whereas TPA synthetic diacylglycerol caused all these when judged...
Glomerular visceral epithelial cells (podocytes) contain interdigitated processes that form specialized intercellular junctions, termed slit diaphragms, which provide a selective filtration barrier in the renal glomerulus. Analyses of disease-causing mutations familial nephrotic syndromes and targeted mutagenesis mice have revealed critical roles several proteins assembly diaphragms. The nephrin–podocin complex is main constituent However, molecular mechanisms regulating these to maintain...
Glyoxalase 1 (GLO1) is a ubiquitous enzyme involved in the detoxification of methylglyoxal, cytotoxic byproduct glycolysis that induces apoptosis. In this study, we found GLO1 gene expression correlates with neoplasm histologic grade (χ2test, p = 0.002) and elevated human basal-like breast cancer tissues. Approximately 90% cancers were 3 tumors highly expressing both stem cell marker ALDH1A3. ALDH1high cells derived from MDA-MB 157 468 lines showed activity. inhibition using TLSC702...
p70 S6 kinase (p70 S6K) has been implicated in the regulation of cell cycle progression. However, mechanism its activation is not fully understood. In present work, evidence provided that an atypical protein C (PKC) isotype, PKCλ, indispensable, but sufficient, for S6K. Both regulatory and domains PKCλ associate directly with Overexpression domain without activity or results suppression serum-induced addition, two types dominant-negative mutants as well a kinase-deficient mutant S6K,...
Altered regulation of insulin secretion by glucose is characteristic individuals with type 2 diabetes mellitus, although the mechanisms that underlie this change remain unclear. We have now generated mice lack λ isoform PKC in pancreatic β cells (βPKCλ–/– mice) and show these animals manifest impaired tolerance hypoinsulinemia. Furthermore, response to high concentrations was impaired, whereas basal rate release increased, islets isolated from βPKCλ–/– mice. Neither cell mass nor islet...
The photoreceptor is a highly polarized neuron and also has epithelial characteristics such as adherens junctions. To investigate the mechanisms of polarity formation cells, we conditionally knocked out atypical protein kinase Cλ ( aPKC λ), which been proposed to play critical role in establishment neuronal polarity, differentiating cells using Cre-loxP system. In λ conditional knock-out (CKO) mice, displayed morphological defects failed form ribbon synapses. Intriguingly, lack...
ABSTRACT Epithelial apicobasal polarity has fundamental roles in epithelial physiology and morphogenesis. The PAR complex, comprising PAR-3, PAR-6 atypical protein kinase C (aPKC), is involved determining cell various biological contexts, including cells. However, it not fully understood how the complex induces polarity. In this study, we found that PAR-3 regulates expression of Girdin (also known as GIV or CCDC88A), a guanine-nucleotide-exchange factor (GEF) for heterotrimeric Gαi subunits,...
During an immune response against a microbial pathogen, activated naive T lymphocytes give rise to effector cells that provide acute host defense and memory long-lived immunity. It has been shown can undergo asymmetric division, enabling the daughter inherit unequal amounts of fate-determining proteins thereby acquire distinct fates from their inception. In this study, we show absence atypical protein kinase C (PKC) isoforms, PKCζ PKCλ/ι, disrupts CD8(+) lymphocyte division. These...
c-Met is a receptor-type tyrosine kinase, which involved in wide range of cellular responses such as proliferation, motility, migration and invasion.It has been reported to be overexpressed various cancers.However, the role breast cancer stem cells (CSCs) still remains unclear.We herein, show that expression significantly elevated Basal-like type comparison with other subtypes.High strongly correlated two CSC markers, ALDH1A3 CD133 cancers.In addition, cancers at tumor stage III-IV...