- Protein Kinase Regulation and GTPase Signaling
- Ubiquitin and proteasome pathways
- Receptor Mechanisms and Signaling
- PI3K/AKT/mTOR signaling in cancer
- Endoplasmic Reticulum Stress and Disease
- 14-3-3 protein interactions
- Mitochondrial Function and Pathology
- Cellular transport and secretion
- Signaling Pathways in Disease
- Histone Deacetylase Inhibitors Research
- Peptidase Inhibition and Analysis
- Cell death mechanisms and regulation
- Glycosylation and Glycoproteins Research
- RNA Research and Splicing
- Muscle Physiology and Disorders
- Pancreatic function and diabetes
- Melanoma and MAPK Pathways
- HER2/EGFR in Cancer Research
- Lung Cancer Treatments and Mutations
- Metabolism, Diabetes, and Cancer
- Alzheimer's disease research and treatments
- Heat shock proteins research
- Nerve injury and regeneration
- Genetics and Neurodevelopmental Disorders
- Augmented Reality Applications
Kitasato University
2025
Kanagawa Prefectural Hospital Organization
2025
Shinshu University
2021-2022
Yakult Honsha (Japan)
2010-2020
Yakult Central Institute
2010-2020
Prefectural University of Hiroshima
2010-2019
Tokushima University
2006-2009
The University of Tokyo
1998-2007
Kanagawa Dental University
2007
SPring-8
2006
Protein kinase C (PKC) isoforms, α, βI, and γ of cPKC subgroup, δ ɛ nPKC ζ aPKC were tyrosine phosphorylated in COS-7 cells response to H 2 O . These isoforms isolated from the -treated showed enhanced enzyme activity various extents. The enzymes, PKC α δ, recovered independent lipid cofactors for their catalytic activity. Analysis mutated molecules that residues, which are conserved domain family, critical activation induced by results suggest can be activated through phosphorylation a...
Cyclic nucleotide phosphodiesterase (PDE) is an important regulator of the cellular concentrations second messengers cyclic AMP (cAMP) and cGMP. Insulin activates 3B isoform PDE in adipocytes a phosphoinositide 3-kinase-dependent manner; however, downstream effectors that mediate signaling to PDE3B remain unknown. Insulin-induced phosphorylation activation endogenous or recombinant 3T3-L1 have now been shown be inhibited by dominant-negative mutant serine-threonine kinase Akt, suggesting Akt...
A wide variety of biological activities including the major metabolic actions insulin is regulated by phosphatidylinositol (PI) 3-kinase. However, downstream effectors various signaling pathways that emanate from PI 3-kinase remain unclear. Akt (protein kinase B), a serine-threonine with pleckstrin homology domain, thought to be one such effector. mutant (Akt-AA) in which phosphorylation sites (Thr308 and Ser473) targeted growth factors are replaced alanine has now been shown lack protein...
Protein kinase B (PKB, also named as Akt or RAC‐protein kinase), that is activated by cellular stress such heat shock and hyperosmotic treatment, was revealed to be oxidative chemical stressors of CdCl 2 NaAsO measuring the activity enzyme immunoprecipitated from transfected COS‐7 cells. Upon a 30‐kDa phosphoprotein co‐immunoprecipitated with PKB cells metabolic labeled [ 32 P]orthophosphate. The identified Hsp27, small protein, immunoblot analysis co‐immunoprecipitation. association Hsp27...
Protein kinase C δ (PKC δ) is normally activated by diacylglycerol produced from receptor-mediated hydrolysis of inositol phospholipids. On stimulation cells with H 2 O , the enzyme tyrosine phosphorylated, a concomitant increase in enzymatic activity. This activation does not appear to accompany its translocation membranes. In present study, phosphorylation sites PKC -treated were identified as Tyr-311, Tyr-332, and Tyr-512 mass spectrometric analysis use precursor-scan method immunoblot...
The LIM domain comprising two zinc-finger motifs is found in a variety of proteins and has been proposed to direct protein-protein interactions. During the identification protein kinase C (PKC)-interacting by yeast two-hybrid assay, novel containing three domains, designated ENH, was shown associate with PKC an isoform-specific manner. Deletion analysis demonstrated that any single ENH associates NH2-terminal region PKC. associated COS-7 cells phosphorylated vitro. Upon treatment phorbol...
The regulation of intracellular localization AFX, a human Forkhead transcription factor, was studied. AFX recovered as phosphoprotein from transfected COS-7 cells growing in the presence FBS, and phosphorylation eliminated by wortmannin, potent inhibitor phosphatidylinositol (PI) 3-kinase. phosphorylated vitro protein kinase B (PKB), downstream target PI 3-kinase, but mutant which three putative sites PKB had been replaced Ala not recognized PKB. In Chinese hamster ovary (CHO-K1) cultured...
Nonessential tRNA modifications by methyltransferases are evolutionarily conserved and have been reported to stabilize mature molecules prevent rapid decay (RTD). The modifying enzymes, NSUN2 METTL1, mammalian orthologs of yeast Trm4 Trm8, which required for protecting against RTD. A simultaneous overexpression METTL1 is widely observed among human cancers suggesting that targeting both proteins provides a novel powerful strategy cancer chemotherapy. Here, we show combined knockdown in HeLa...
We expressed delta subspecies of protein kinase C (delta-PKC) fused with green fluorescent (GFP) in CHO-K1 cells and observed the movement this fusion living after three different stimulations. The delta-PKC-GFP had enzymological characteristics very similar to those native delta-PKC was present throughout cytoplasm cells. ATP at 1 mM caused a transient translocation plasma membrane approximately 30 s stimulation sequent retranslocation within 3 min. A tumor-promoting phorbol ester,...
It has been shown that inhibition of phosphatidylinositol (PI) 3-kinase blocks neurite outgrowth PC12 cells stimulated with nerve growth factor. To further assess the role PI 3-kinase, active form was expressed in by adenovirus mediated introduction a site-specific recombinase, Cre. After expression elevation levels 3,4-diphosphate and 3,4,5-trisphosphate as well formation neurite-like processes observed. The process inhibited wortmannin, selective inhibitor which suggests high activity...
ABSTRACT We have previously shown that sustained phosphatidylinositol (PI)-3 kinase activity is necessary for neurite outgrowth of PC12 cells induced by nerve growth factor (NGF). Microinjection a constitutively active mutant PI-3 process formation suggesting indeed involved in the outgrowth. However, processes appeared to be incomplete neurites as they had very poor organization F-actin and GAP43 antigen. The microtubule network was enhanced process-bearing inhibited colchicine microtubules...
Involvement of Akt/Protein kinase B (PKB), a serine/threonine with pleckstrin-homology domain, in angiotensin II (ANG II)-induced signal transduction was investigated cultured vascular smooth muscle cells (VSMC). Stimulation the ANG led to marked increase activity Akt/PKB, which coincided Ser-473 phosphorylation. II-stimulated Akt/PKB activation rapid, concentration dependent, and inhibited by AT 1 -receptor antagonist CV-11974, but not pertussis toxin. stimulated Ca 2+ ionophore ionomycin,...
Adaptor proteins for the various growth factor receptors play a crucial role in signal transduction through tyrosine phosphorylation. Several candidates adaptor with potential effects on epidermal (EGF) receptor-mediated signaling pathway have been identified by recent phosphoproteomic studies. Here, we focus novel protein, GAREM (Grb2-associated and regulator of Erk/MAPK) as downstream molecule EGF receptor. is phosphorylated at 105 453 after stimulation. Grb2 was its binding partner,...
Grb2-associated regulator of Erk/MAPK1 (GAREM) is an adaptor molecule in the EGF-mediated signaling pathway. GAREM expressed ubiquitously human organs and cultured cells. Two homologues are encoded by genome. Therefore, previously identified named GAREM1. Here we characterized a new subtype GAREM, GAREM2, that specifically mouse, rat, brain. Three GAREM2 tyrosines (Tyr-102, Tyr-429, Tyr-551) phosphorylated upon EGF stimulation necessary for binding to Grb2. Furthermore, Shp2 regulate Erk...
Protein kinase B (PKB) is a downstream target of phosphatidylinositol (PI) 3-kinase in the signaling pathway growth factors, and activated by cellular stress such as H(2)O(2) heat shock. To study mechanism stress-induced activation PKB, PI products were measured stress-stimulated cells. Both 3,4-bisphosphate 3,4, 5-trisphosphate increased H(2)O(2)-treated cells, elevation these phospholipids PKB concurrently blocked wortmannin, potent inhibitor 3-kinase. In heat-shocked level did not change...
The ligand-mediated down-regulation of the growth factor receptors is preceded by involvement various other factors. In particular, a ubiquitin ligase, Cbl, plays central role in this event. Several candidates that have potential effects on negative control epidermal (EGF) receptor now been identified our recent studies phospho-proteomics. Among these molecules, we focus characterizing novel protein, Ymer, which tyrosine-phosphorylated and ubiquitinated protein. Ymer found to be...