- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Galectins and Cancer Biology
- Growth Hormone and Insulin-like Growth Factors
- Proteoglycans and glycosaminoglycans research
- Cancer, Hypoxia, and Metabolism
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Ubiquitin and proteasome pathways
- Developmental Biology and Gene Regulation
- Genetics and Neurodevelopmental Disorders
- Sexual Differentiation and Disorders
- Studies on Chitinases and Chitosanases
- RNA modifications and cancer
- Neurobiology and Insect Physiology Research
- Metabolism, Diabetes, and Cancer
- Protein Tyrosine Phosphatases
- Cellular transport and secretion
- Invertebrate Immune Response Mechanisms
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Skin Diseases and Diabetes
- Hormonal Regulation and Hypertension
- GABA and Rice Research
- Hedgehog Signaling Pathway Studies
- Congenital limb and hand anomalies
Nagoya University
2014-2023
Nagahama Institute of Bio-Science and Technology
2011-2015
Minamiaoyama Eye Clinic
1999-2002
Foundation for Growth Science
1993-1997
University of Florida
1993
The glycosyltransferase EOGT transfers O-GlcNAc to a consensus site in epidermal growth factor-like (EGF) repeats of limited number secreted and membrane proteins, including Notch receptors. In EOGT-deficient cells, the binding DLL1 DLL4, but not JAG1, canonical ligands was reduced, ligand-induced signaling impaired. Mutagenesis sites on NOTCH1 also resulted decreased DLL4. functions were investigated retinal angiogenesis that depends signaling. Global or endothelial cell-specific deletion...
Extracellular O-GlcNAc is a novel class of modification catalyzed by epidermal growth factor-like (EGF)-domain specific transferase (EOGT). In mammals, EOGT required for ligand-mediated Notch signaling vascular development. Previous studies have revealed that in mammalian cultured cells subject to subsequent glycosylation, which may impose additional layers regulation. This study aimed analyze the glycans Drosophila EGF20 as model substrates and mouse Notch1 EGF repeats mass-spectrometry....
Epidermal growth factor (EGF) domain-specific O-linked N-acetylglucosamine (EOGT) is an endoplasmic reticulum (ER)-resident (O-GlcNAc) transferase that acts on EGF domain-containing proteins such as Notch receptors. Recently, mutations in EOGT have been reported patients with Adams-Oliver syndrome (AOS). Here, we characterized enzymatic properties of mouse and mutants associated AOS. Simultaneous expression Notch1 repeats human embryonic kidney 293T (HEK293T) cells led to immunoreactivity...
To investigate mechanisms for increased malignant properties in melanomas by ganglioside GD3, enzyme-mediated activation of radical sources and subsequent mass spectrometry were performed using an anti-GD3 antibody GD3-positive (GD3+) GD3-negative (GD3-) melanoma cell lines. Neogenin, defined as a GD3-neighbored molecule, was largely localized lipid/rafts GD3+ cells. Silencing neogenin resulted the reduction growth invasion activity. Physical association between GD3 demonstrated...
Notch signaling receptors, ligands, and their downstream target genes are dysregulated in pancreatic ductal adenocarcinoma (PDAC), suggesting a role of tumor development progression. However, dysregulation by post-translational modification receptors remains poorly understood. Here, we analyzed the Notch-modifying glycosyltransferase involved regulation ligand-dependent pathway. Bioinformatic analysis revealed that expression epidermal growth factor (EGF) domain-specific O-linked...
Mitochondria perform multiple functions critical to the maintenance of cellular homeostasis. Here we report that downregulation histone deacetylase 6 (HDAC6) causes a reduction in net activity mitochondrial enzymes, including respiratory complex II and citrate synthase. HDAC6 ubiquitin‐binding activities were both required for recovery reduced metabolic due loss HDAC6. Hsp90, substrate HDAC6, localizes mitochondria partly mediates regulation by Our finding suggests regulates metabolism might...
O-GlcNAc modification of Notch receptors regulates ligand interactions in a manner distinct from other forms O-glycans on epidermal growth factor (EGF)-like repeats receptors. Although many proteins, besides receptors, are expected to be O-GlcNAcylated by EGF domain-specific transferase (EOGT), only small number proteins have been reported modified vivo, and elongated glycans not extensively explored. To extend our view the specificity variety glycan modification, we conducted comprehensive...
Epidermal growth factor (EGF) domain-specific O-GlcNAc transferase (EOGT) is an endoplasmic reticulum (ER)-resident protein that modifies EGF repeats of Notch receptors and thereby regulates Delta-like ligand-mediated signaling. Several EOGT mutations may affect putative N-glycosylation consensus sites are recorded in the cancer database, but presence function N-glycans have not yet been characterized. Here, we identified mouse elucidated their molecular functions. Three predicted sequences...
Patients with Turner syndrome have many somatic characteristics, including short stature. We report the results of a 6-year multicentre clinical trial recombinant human growth hormone (GH) therapy in 63 patients syndrome. Twenty-six received GH at dose 0.5 IU/kg/week, while 37 GH, 1.0 by daily subcutaneous injection. At start treatment, there was no significant difference between two groups chronological age, bone height or rate. Both treatment showed increase during treatment. The current...
Clinical trials of human GH (hGH) therapy in Turner's syndrome were started 1986. Between 1986 and 1990. 362 patients enrolled; 115 treated for more than 6 years. The age at the start treatment ranged from 5 to 18 years (mean 10 years). Fifty-one received hGH a weekly dosage 0.5 IU/kg 64 1.0 by daily s.c. injection. Both groups showed statistically significant growth increase during initial 4 treatment. rate height was significantly greater 2 with high dose low dose. increases over...
OBJECTIVE: To report on growth pattern and body proportion in the combination of short stature homeobox-containing gene (SHOX) overdosage gonadal estrogen deficiency. DESIGN: Auxological studies a 20-year-old Japanese female with 45,X[28]/46,X,psu idic(X)(q28)[72], deficiency, SHOX duplication idic(X) chromosome, who received sex steroid replacement therapy from 16 years 8 months age. METHODS: Growth were assessed by age-matched standards for females. RESULTS: She continued to grow mean...
Data for a total of 942 new cases hypopituitarism, out 3493 patients treated with recombinant human growth hormone (GH) more than 1 year, have been analysed. The mean peak GH correlated well clinical variables related to and was considered be good index secretory capacity. Mean inversely obesity ( r = ‐0.253, p < 0.01). lower the height velocity before treatment, SDS, greater therapeutic effect achieved. less or equal 5 ng/ml were defined as having complete deficiency (GHD), those 5‐10...
Patients with Turner syndrome were treated recombinant human growth hormone (GH) for 3 years. Sixty-eight patients received GH, 0.5 IU/kg/week, while 93 1.0 by daily subcutaneous injection. Both treatment groups showed a statistically significant increase in during treatment. However, the higher dose increased height velocity to significantly greater extent first and second year of The projected adult was exceeded 52 71 over age 14 Plasma insulin-like factor 1 levels elevated no remarkable...
We report a Japanese boy with IGHD who is compound heterozygote at the GH-1 gene locus. The patient and his mother were heterozygous for 6.7 kb deletion of gene. A T-->C transition position -123, an A-->G -6 A-->T -1 in promoter region addition AGAA base 250 intron I observed one allele father. These results demonstrate that familial heterogeneous disease perturbs different steps expression