A5019076098- Protein Kinase Regulation and GTPase Signaling
- PI3K/AKT/mTOR signaling in cancer
- Cellular transport and secretion
- Cell Adhesion Molecules Research
- Wnt/β-catenin signaling in development and cancer
- Monoclonal and Polyclonal Antibodies Research
- Caveolin-1 and cellular processes
- Drug Transport and Resistance Mechanisms
- Cancer-related Molecular Pathways
- Glycosylation and Glycoproteins Research
- Microtubule and mitosis dynamics
- TGF-β signaling in diseases
- Phagocytosis and Immune Regulation
- Cellular Mechanics and Interactions
- Cancer Cells and Metastasis
- Hippo pathway signaling and YAP/TAZ
- Autophagy in Disease and Therapy
- Cytokine Signaling Pathways and Interactions
- CRISPR and Genetic Engineering
- Ubiquitin and proteasome pathways
- T-cell and B-cell Immunology
- Pluripotent Stem Cells Research
- Protein Tyrosine Phosphatases
- RNA Research and Splicing
- Mast cells and histamine
Osaka University
2013-2024
Menoufia University
2015
Japan Science and Technology Agency
2000-2005
Ehime University
2005
Japan Research Institute
2005
Nagahama Institute of Bio-Science and Technology
2005
Science and Technology Corporation (United States)
2005
Centre for Research in Engineering Surface Technology
2005
Center for Responsible Travel
2005
The University of Tokyo
1993-2004
The functions of src family protein-tyrosine kinases are thought to be regulated negatively by the phosphorylation highly conserved tyrosine residues close their carboxyl termini. Recently we have purified and cloned a kinase (designated as CSK) that can specifically phosphorylate negative regulatory site p60c-src. To elucidate relationship between CSK other types kinases, investigated tissue distribution examined whether could sites than Western blot analysis indicated was enriched at...
Mammalian target of rapamycin (mTOR) is a kinase that plays key role in wide array cellular processes and exists two distinct functional complexes, mTOR complex 1 (mTORC1) 2 (mTORC2). Although mTORC2 primarily activated by growth factors, mTORC1 regulated numerous extracellular intracellular signals such as nutrients, redox. Previous study has shown cysteine oxidants sufficiently activate activity under amino acid-depleted conditions reducing agent effectively suppresses acid-induced...
Abstract Macrophages play crucial roles in host defence and tissue homoeostasis, processes which both environmental stimuli intracellularly generated metabolites influence activation of macrophages. Activated macrophages are classified into M1 M2 It remains unclear how intracellular nutrition sufficiency, especially for amino acid, influences on macrophage activation. Here we show that a lysosomal adaptor protein Lamtor1, forms an amino-acid sensing complex with vacuolar-type H + -ATPase...
CD151, one of the tetraspanins, forms a stable complex with integrin alpha3beta1, major laminin receptor on cell surface. We found that 8C3, an anti-CD151 mAb obtained by screening for reactivity alpha3beta1-CD151 complexes, was capable dissociating CD151 from thereby allowing us to deplete purified complexes. The CD151-free alpha3beta1 thus showed significant reduction in its ability bind laminin-10/11, high-affinity ligand concomitant AG89, which recognizes activated beta1-containing...
The carboxyl-terminal Src kinase (Csk) is an indispensable negative regulator for the family tyrosine kinases (SFKs) that play pivotal roles in various cell signalings. To understand molecular basis of Csk-mediated regulation SFKs, we elucidated crystal structure full-length Csk. Csk consists six molecules classified as active or inactive states according to coordinations catalytic residues. assembles SH2 and SH3 domains differently from their binding pockets are oriented outward enabling...
The mechanistic target of rapamycin (mTOR) functions as a component two large complexes, mTORC1 and mTORC2, which play crucial roles in regulating cell growth homeostasis. However, the molecular mechanisms by mTOR controls proliferation remain elusive. Here we show that FoxO3a transcription factor is coordinately regulated plays role controlling proliferation. To dissect signaling, was specifically inactivated depleting p18, an essential anchor on lysosomes. inactivation caused marked...
ABSTRACT In response to amino acid supply, mTORC1, a master regulator of cell growth, is recruited the lysosome and activated by small GTPase Rheb. However, intracellular localization Rheb controversial. this study, we showed that significant portion localized on Golgi but not lysosome. GFP–Rheb could activate even when forced exclusively localize Golgi. Likewise, artificial recruitment mTORC1 allowed its activation. Accordingly, was in contact with at an newly discovered area term...
The mechanistic target of rapamycin complex 1 (mTORC1) plays a central role in regulating cell growth and metabolism by responding to cellular nutrient conditions. activity mTORC1 is controlled Rag GTPases, which are anchored lysosomes via Ragulator, pentameric protein consisting membrane-anchored p18/LAMTOR1 two roadblock heterodimers. Here we report the crystal structure Ragulator with domains RagA-C, helps elucidate molecular basis for regulation GTPases. In structure, p18 wraps around...
Cloning and sequencing of chicken C-terminal Src kinase (CSK), a tyrosine that phosphorylates the regulatory residue present on cytoplasmic kinases family, demonstrated high degree interspecies conservation as well src homology 2 3 domains N-terminal to domain. The lack autophosphorylation sites distinguishes CSK from other kinases. is unique does not belong gene suggesting it may phosphorylate members family in addition c-Src. Since complex formation between c-Src seemed likely step control...
Necdin is a multifunctional signaling protein that stabilizes terminal differentiation of postmitotic neurons. The human necdin gene in chromosome 15q11-q12 maternally imprinted, paternally transcribed, and not expressed Prader-Willi syndrome, genomic imprinting-associated neurodevelopmental disorder. Although necdin-deficient mice display several abnormal phenotypes reminiscent this little known about molecular mechanisms lead to the defects. Here, we demonstrate required for physiological...
For the zonula adherens (ZA) to be established by linear arrangement of junctions (AJs) in epithelial sheet cells, critical for cell formation and intercellular barrier function, myosin-2 is supposedly integrated into ZA with result overlapping localization E-cadherin/actin/myosin-2. Here, we immunofluorescently showed that failed cultured epithelial-type ZO1(ko)/2(kd) Eph4 cells lacking ZO-1 -2 (zonula occludens-1 -2) knockout knockdown, respectively. Instead, a linearized but fragmented...
Bacterial Tn10-encoded metal-tetracycline/H<sup>+</sup> antiporter was the first found drug exporter and has been studied as a paradigm of antiporter-type major facilitator superfamily transporters. Here 400 amino acid residues this protein were individually replaced by cysteine except for initial methionine. As result, we could obtain complete map functionally or structurally important residues. In addition, determine precise boundaries all transmembrane segments on basis reactivity...
The Src-like protein-tyrosine kinase Fyn is associated with T-cell antigen receptor. Transient expression of actively mutated Fyn, having Phe-528 instead Tyr-528 or Thr-338 Ile-338, in Jurkat T-cells stimulated the serum response element (SRE), 12-O-tetradecanoyl-phorbol-13-acetate element, cyclic AMP and c-fos promoter. stimulation SRE was particularly prominent not only active but also normal (wild-type) Fyn. by both Lck. Furthermore, transcription from IL-2 gene promoter when transfected...
ABCA5 is a member of the ABC transporter A subfamily, and mouse orthologue (mABCA5) in newborn brain neural cells was identified by reverse transcription-PCR.Full-length cDNA cloning revealed that mABCA5 consists 1,642 amino acid residues its putative structure full-type having two sets six transmembrane segments nucleotide binding domain.Immunohistochemical studies expressed brain, lung, heart, thyroid gland.A subcellular localization analysis showed resident lysosomes late endosomes.Abca5...
Podosomes and invadopodia are actin-rich membrane protrusions that play a crucial role in cell adhesion migration, extracellular matrix remodeling normal cancer cells. The formation of podosomes is promoted by upregulation some oncogenic molecules closely related to the invasive potential However, molecular mechanisms underlying podosome invadopodium still remain unclear. Here, we show guanine nucleotide exchange factor (GEF) for Rho family GTPases (Arhgef5) Src-induced formation. Using an...
Multidrurg resistance-associated protein 2 (MRP2)/canalicular multispecific organic anion transporter (cMOAT) is involved in the ATP-dependent export of anions across bile canalicular membrane. To identify functional amino acid residues that play essential roles substrate transport, each 13 basic around transmembrane regions (TMs) 6–17 were replaced with alanine. Wild type and mutant proteins expressed COS-7 cells, transport activity was measured as excretion glutathione-methylfluorescein....
Cbp, a C-terminal Src kinase (Csk)-binding protein, is transmembrane phosphoprotein that has been implicated in the regulation of family (SFK) through recruiting Csk, negative regulator SFK, to membrane microdomain lipid rafts. To examine contribution Cbp cell adhesion signaling mediated by we investigated responsible for phosphorylating and mode phosphorylation during process. The results obtained using mutant mice or cells lack Csk and/or member Fyn, reveal phosphorylated predominantly...