T Kawasaki

Kyoto University, Kioto, Kyōto, Japan

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Publications (148)462.45 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    ChemInform 01/2010; 29(8).
  • Takeshi Kawasaki, Tetsutaro Kimachi
    [Show abstract] [Hide abstract]
    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    ChemInform 01/2010; 30(38).
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    ABSTRACT: Leucine zipper-bearing kinase (LZK) is a novel member of the mixed lineage kinase (MLK) protein family, the cDNA of which was first cloned from a human brain cDNA library [Sakuma, H., Ikeda, A., Oka, S., Kozutsumi, Y., Zanetta, J.-P., and Kawasaki, T. (1997) J. Biol. Chem. 272, 28622-28629]. Several MLK family proteins have been proposed to function as MAP kinase kinase kinases in the c-Jun NH(2) terminal kinase (JNK)/stress-activated protein kinase (SAPK) pathway. In the present study, we demonstrated that, like other MLKs, LZK activated the JNK/SAPK pathway but not the ERK pathway. LZK directly phosphorylated and activated MKK7, one of the two MAPKKs in the JNK/SAPK pathway, to a comparable extent to a constitutive active form of MEKK1 (MEKK1DeltaN), suggesting a biological role of LZK as a MAPKKK in the JNK/SAPK pathway. Recent studies have revealed the essential roles of scaffold proteins in intracellular signaling pathways including MAP kinase pathways. JIP-1, one of the scaffold proteins, has been shown to be associated with MLKs, MKK7, and JNK [Whitmarsh, A.J., Cavanagh, J., Tournier, C., Yasuda, J., and Davis, R.J. (1998) Science 281, 1671-1674], suggesting the presence of a selective signaling pathway including LZK, MKK7, and JNK. Consistent with this hypothesis, we provided evidence that LZK is associated with the C-terminal region of JIP-1 through its kinase catalytic domain. In addition, LZK-induced JNK activation was markedly enhanced when LZK and JNK were co-expressed with JIP-1. These results constituted important clues for understanding the molecular mechanisms regulating the signaling specificities of various JNK activators under different cellular conditions.
    Journal of Biochemistry 01/2002; 130(6):773-81. · 3.07 Impact Factor
  • T Kawasaki, S Oka
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    ABSTRACT: The HNK-epitope, 3-sulfo-glucuronyl residue is expressed specifically on a series of cell adhesion molecules and on some glycolipids in the nervous system over a wide range of species, and its expression is spatially and temporally regulated during the development of the nervous system. To study the biological functions of the epitope, we have cloned the enzymes that are involved in the biosynthesis of the epitope, glucuronyltransferase (GlcAT-P and GlcAT-S) and sulfotransferase (Sulf-T), A Northern blot analysis of GlcAT mRNAs in various rat tissues indicated that GlcAT-P and -S are the brain-specific or neural-specific enzymes. Upon transfection of the full length GlcAT-P cDNA into COS-1 cells, which do not express the HNK-lepitope, cells were transformed into HNK-1 positive cells. These cells showed dramatic changes of the cell architecture. They had long and branched processes with irregular shapes and several micro spikes on the soma and processes. Another function of the HNK-1 epitope is the inhibition of cell-cell aggregation. Thus control COS-1 cells formed huge aggregates after incubation at room temperature for 90 min, and most of the HNK-1 positive cells remained as free single cells.
    Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology 10/2001; 21(3):95-9.
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    ABSTRACT: The human plasma protein mannan-binding lectin (MBL) is an essential part of the innate immune defense system. Low levels of MBL are associated with recurrent infections and other clinically significant signs of a compromised immune defense. Previous studies have addressed the possibility of reconstitution therapy by the use of recombinant or plasma-derived protein. Natural MBL is a multimeric protein, which consists of up to 18 identical polypeptide chains. Synthesis by in vitro methods of MBL with the proper multimeric structure is difficult. We here report that mice obtain MBL levels comparable to those found in normal human plasma when injected with an MBL expression construct as naked plasmid DNA contained in a large volume of physiologic salt solution. The expression was confined to the liver and high MBL expression levels were obtained with less than 5% of the liver cells transfected. The multimeric structure of the MBL found in plasma of injected mice was similar to that of natural MBL. Thus, liver expression following injection of naked DNA is an alternative to reconstitution therapy with a protein having a complex quaternary structure.
    Molecular Therapy 07/2001; 3(6):867-74. · 7.04 Impact Factor
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    ABSTRACT: In our previous study, the sphingosine-like immunosuppressant ISP-1 was shown to induce apoptosis in the mouse cytotoxic T cell line CTLL-2. In this study, we characterized the ISP-1-induced apoptotic pathway. Although caspase-3-like protease activity increases concomitantly with ISP-1-induced apoptosis in CTLL-2 cells, the apoptosis is not inhibited by caspase-3-like protease inhibitors, i.e. DEVD-cho and z-DEVD-fmk. In contrast, sphingosine-induced apoptosis in CTLL-2 cells is caspase-3-like protease-dependent. A caspase inhibitor with broad specificity, z-VAD-fmk, protects cells from apoptosis induced by ISP-1, indicating that ISP-1-induced apoptosis is dependent on caspase(s) other than caspase-3. Overexpression of Bcl-2 or Bcl-xL suppresses the apoptosis induced by ISP-1, although sphingosine-induced apoptosis is not efficiently inhibited by Bcl-2. Finally, ISP-1-induced mitochondrial depolarization, which is thought to be a checkpoint dividing the apoptotic pathway into upstream and downstream stages, is not inhibited by DEVD-cho, but is inhibited by z-VAD-fmk. These data suggest that a pathway dependent on caspase(s) other than caspase-3 is involved upstream of mitochondrial depolarization in ISP-1-induced apoptosis.
    Journal of Biochemistry 05/2001; 129(4):521-7. · 3.07 Impact Factor
  • R Katsuyama, A Morioka, S Oka, T Kawasaki
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    ABSTRACT: Macrophage asialoglycoprotein-binding protein (M-ASGP-BP) is a Gal/GalNAc-specific lectin, which functions as an endocytosis receptor. We found that the expression of M-ASGP-BP mRNA in bone marrow cells was induced during the differentiation into macrophages. To investigate the mechanism by which M-ASGP-BP mRNA expression is induced, we used U937 cells as a model. Treatment of U937 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in M-ASGP-BP mRNA expression within 6 h. This induction was completely inhibited by PKC inhibitors, calphostin C, and staurosporine. Furthermore, MAP kinase inhibitors PD98059, but not SB202190, blocked M-ASGP-BP mRNA expression. These data indicate that M-ASGP-BP mRNA expression occurs through the activation of PKC and the MAPK classical pathway in the course of cell differentiation into macrophages.
    Biochemical and Biophysical Research Communications 03/2001; 280(5):1269-73. · 2.28 Impact Factor
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    ABSTRACT: The mixed lineage kinase (MLK) family is a recently described protein kinase family. The MLKs contain a kinase domain followed by a dual leucine zipper-like motif. We previously reported the molecular cloning of LZK (leucine zipper-bearing kinase), a novel MLK, and that LZK activated the c-Jun NH2 terminal kinase (JNK)/stress-activated protein kinase (SAPK) pathway through MKK7 in cells. Here, we reveal that LZK forms dimers/oligomers through its dual leucine zipper-like motif, and that this is necessary for activation of the JNK/SAPK pathway. We also identify the C-terminal functional region of LZK, which is indispensable for the activation of SEK1, but not that of MKK7.
    FEBS Letters 02/2001; 488(3):190-5. · 3.58 Impact Factor
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    ABSTRACT: The acceptor specificity of a rat brain glucuronyltransferase, GlcAT-P, associated with biosynthesis of the HNK-1 epitope on glycoproteins, was investigated using asialoorosomucoid as a model acceptor substrate. Structural analysis of N-linked oligosaccharides, to which glucuronic acid was transferred by GlcAT-P, by means of two-dimensional mapping of pyridylamino-oligosaccharides and MS spectrometry, demonstrated that the enzyme transferred glucuronic acid to bi-, tri-, and tetra-antennary complex type sugar chains, with almost equal efficiency, indicating that the enzyme has no preference as to the number of acceptor sugar branches. Next, we studied the branch specificity of this enzyme by means of the selective branch scission method involving two step exoglycosidase digestion using authentic pyridylamino-oligosaccharides. The GlcAT-P is highly specific for the terminal N-acetyllactosamine structure and no glucuronic acid was incorporated into a Galbeta1-3GlcNAc moiety. The GlcAT-P transferred glucuronic acid to the galactose residues in the N-acetyllactosamine branches of bi-, tri-, and tetra-antennary oligosaccharide chains, with different efficiencies and most preferentially to those in the Galbeta1-4GlcNAcbeta1-4Manalpha1-3 branch.
    Glycoconjugate Journal 01/2001; 17(12):877-85. · 1.88 Impact Factor
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    ABSTRACT: Specificities of three mouse major histocompatibility complex (MHC) class I molecules, Kb, Db, and Ld, were analyzed by positional scanning using combinatorial peptide libraries. The result of the analysis was used to create a scoring program to predict MHC-binding peptides in proteins. The capacity of the scoring was then challenged with a number of peptides by comparing the prediction with the experimental binding. The score and the experimental binding exhibited a linear correlation but with substantial deviations of data points. Statistically, for approximately 80% of randomly chosen peptides, MHC-binding capacity could be predicted within one log concentration of peptides for a half-maximal binding. Known cytotoxic T-lymphocyte epitope peptides could be predicted, with a few exceptions. In addition, frequent findings of MHC-binding peptides with incomplete or no anchor amino acid(s) suggested a substantial bias introduced by natural antigen processing in peptide selection by MHC class I molecules.
    Immunogenetics 09/2000; 51(10):816-28. · 2.89 Impact Factor
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    ABSTRACT: All members of a glucuronyltransferase (GlcAT) gene family cloned to date contain four conserved regions (modules I-IV), which are widely located in the catalytic domain. In order to understand the biological significance of these modules, we investigated the structure-function relationship of GlcAT-P by means of the combination of site-directed mutagenesis and computer aided three-dimensional modeling. The wild-type and mutant GlcAT-Ps were expressed in Escherichia coli as glutathione-S-transferase (GST)-fused soluble proteins. Most of the mutants in which a polar amino acid within the modules was replaced with alanine lost their transferase activity almost completely, while all of the mutants in which the replacement was outside these modules retained the original catalytic activity. A three-dimensional (3-D) model of GlcAT-P was constructed by computer simulation with the three-dimensional structure of adenylate kinase (1AKE) as a template. This model predicted that the large catalytic domain of GlcAT-P forms a globular shape with a Rossmann-fold motif consisting of five alpha-helix and beta-sheet repeats. The putative catalytic pocket consisting mainly of modules I-III is surrounded by a cluster of polar amino acids, which are essential for the transferase activity and also for the binding to the acceptor substrate (essential amino acids), asialo-orosomucoid. There is the second cluster of essential amino acids almost on the opposite surface of the molecule, in which an aspartic acid repeat (DDD) is located. The biological significance of the second cluster is currently not clear but it may be associated with the interaction of the enzyme with modulation molecules, manganese and membrane phospholipids.
    Journal of Biochemistry 09/2000; 128(2):283-91. · 3.07 Impact Factor
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    ABSTRACT: ISP-1 is a new type of immunosuppressant, the structure of which is homologous to that of sphingosine. In a previous study, ISP-1 was found to inhibit mammalian serine palmitoyltransferase, the primary enzyme involved in sphingolipid biosynthesis, and to reduce the intracellular pool of sphingolipids. ISP-1 induces the apoptosis of cytotoxic T cells, which is triggered by decreases in the intracellular levels of sphingolipids. In this study, the inhibition of yeast (Saccharomyces cerevisiae) proliferation by ISP-1 was observed. This ISP-1-induced growth inhibition was also triggered by decreases in the intracellular levels of sphingolipids. In addition, DNA duplication without cytokinesis was detected in ISP-1-treated yeast cells on flow cytometry analysis. We have cloned multicopy suppressor genes of yeast which overcome the lethal sphingolipid depletion induced by ISP-1. One of these genes, SLI2, is synonymous with YPK1, which encodes a serine/threonine kinase. Kinase-dead mutants of YPK1 did not show any resistance to ISP-1, leading us to predict that the kinase activity of the Ypk1 protein should be essential for this resistance to ISP-1. Ypk1 protein overexpression had no effect on sphingolipid biosynthesis by the yeast. Furthermore, both the phosphorylation and intracellular localization of the Ypk1 protein were regulated by the intracellular sphingolipid levels. These data suggest that the Ypk1 protein is a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. The Ypk1 protein was reported to be a functional homologue of the mammalian protein kinase SGK, which is a downstream kinase of 3-phosphoinositide-dependent kinase 1 (PDK1). PDK1 phosphotidylinositol (PI) is regulated by PI-3,4,5-triphosphate and PI-3,4-bisphosphate through the pleckstrin homology (PH) domain. Overexpression of mammalian SGK also overcomes the sphingolipid depletion in yeast. Taking both the inability to produce PI-3,4, 5-triphosphate and PI-3,4-bisphosphate and the lack of a PH domain in the yeast homologue of PDK1, the Pkh1 protein, into account, these findings further suggest that yeast may use sphingolipids instead of inositol phospholipids as lipid mediators.
    Molecular and Cellular Biology 07/2000; 20(12):4411-9. · 5.37 Impact Factor
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    ABSTRACT: Although a number of cellular components of cytokinesis have been identified, little is known about the detailed mechanisms underlying this process. Here, we report that the lipid metabolite psychosine (galactosylsphingosine), derived from galactosylceramide, induced formation of multinuclear cells from a variety of nonadherent and adherent cells due to inhibition of cytokinesis. When psychosine was added to the human myelomonocyte cell line U937, which was the most sensitive among the cell lines tested, cleavage furrow formed either incompletely or almost completely. However, abnormal contractile movement was detected in which the cellular contents of one of the hemispheres of the contracting cell were transferred into its counterpart. Finally, the cleavage furrow disappeared and cytokinesis was reversed. Psychosine treatment also induced giant clots of actin filaments in the cells that probably consisted of small vacuoles with filamentous structures, suggesting that psychosine affected actin reorganization. These observations could account for the formation of multinuclear globoid cells in the brains of patients with globoid cell leukodystrophy, a neurological disorder characterized by the accumulation of psychosine due to galactosylceramidase deficiency.
    The Journal of Cell Biology 06/2000; 149(4):943-50. · 10.82 Impact Factor
  • T Kawasaki
    Biochimica et Biophysica Acta 01/2000; 1473(1):186-95. · 4.66 Impact Factor
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    ABSTRACT: Serum mannan binding protein (MBP), a mannose/N-acetylglusosamine-specific lectin, is important in innate immunity. In order to elucidate the mechanism underlying the wide intra- and interracial variety in the MBP serum level, we have studied the transcriptional regulation of human MBP. Rapid amplification of cDNA ends (5' RACE) analysis of Hep G2 RNA indicated the presence of a novel exon, designated as "exon 0," upstream of previously identified exon 1 [Taylor, M.E. et al. (1989) Biochem. J. 262, 763-771]. Two MBP mRNAs with different sized 5'-noncoding regions were detected: the longer transcript starts at exon 0 and the shorter one at exon 1. Promoter analysis involving a luciferase assay vector revealed that the transcript starting from exon 1 predominates over that starting from exon 0. In addition, a hepatocyto-specific nuclear factor, (HNF)-3, which is known to control the expression of hepatocyto-specific genes, up-regulates the transcription of human MBP from exon 1, while a glucocorticoid, which is known to up-regulate acute phase proteins, markedly suppresses MBP transcription. Recently, polymorphisms were found to occur in the promoter region at two positions [Madsen, H.O. et al. (1995) J. Immunol. 155, 3013-3020]. Functional promoter analysis indicated that three haplotype variants as to these positions, HY, LY, and LX, exhibit high, medium and low promoter activity, respectively, in accordance with the results of a previous population study.
    Journal of Biochemistry 01/2000; 126(6):1004-12. · 3.07 Impact Factor
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    ABSTRACT: We characterized the recombinant glucuronyltransferase I (GlcAT-I) involved in the glycosaminoglycan-protein linkage region biosynthesis. The enzyme showed strict specificity for Galbeta1-3Galbeta1-4Xyl, exhibiting negligible incorporation into other galactoside substrates including Galbeta1-3Galbeta1-O-benzyl, Galbeta1-4GlcNAc and Galbeta1-4Glc. A comparison of the GlcAT-I with another beta1,3-glucuronyltransferase involved in the HNK-1 epitope biosynthesis revealed that the two beta1,3-glucuronyltransferases exhibited distinct and no overlapping acceptor substrate specificities in vitro. Nevertheless, the transfection of the GlcAT-I cDNA into COS-1 cells induced the significant expression of the HNK-1 epitope. These results suggested that the high expression of the GlcAT-I gene rendered the cells capable of synthesizing the HNK-1 epitope.
    FEBS Letters 11/1999; 459(3):415-20. · 3.58 Impact Factor
  • H Naito, Y Ma, K Uemura, Y Arano, T Kawasaki
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    ABSTRACT: Human mannan-binding protein (MBP) is a serum lectin involved in innate immunity. MBP activates the complement pathway through its interaction with mannose-rich carbohydrates on various microorganisms and a common opsonic defect has been shown to be associated with a low serum concentration of MBP. This low serum concentration is closely associated with a single base mutation in codon 52, 54 or 57 of the human MBP gene, which results in a change of Arg52 to Cys, Gly54 to Asp, or Gly57 to Gln, respectively, in the collagen-like region of the molecule and prevents the formation of higher oligomers. However, the mechanism underlying the low serum concentration in such patients is completely unknown. The levels of protein synthesis and secretion of the normal and mutant MBPs seem to be similar according to our previous in vitro results. In this study, we examined the plasma clearance of the normal and mutant human (Gly54Asp) MBPs in mice, and found that the half-life of the mutant MBP is about half that of the normal MBP, explaining in part the difference in the plasma levels between the two types of MBP.
    Biochemical and Biophysical Research Communications 04/1999; 256(1):231-4. · 2.28 Impact Factor
  • T Seiki, S Oka, K Terayama, K Imiya, T Kawasaki
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    ABSTRACT: A cDNA encoding a novel glucuronyltransferase was cloned from a rat brain cDNA library. The cDNA sequence contained an open reading frame encoding 324 amino acids, with type II transmembrane topology. The amino acid sequence revealed 49% homology to rat GlcAT-P, a glucuronyltransferase involved in the biosynthesis of the HNK-1 carbohydrate epitope of glycoproteins, [Terayama et al. (1997) Proc. Natl. Acad. Sci. USA 94, 6093-6098] and the highest sequence homology was found in the catalytic region. Northern blot analysis indicated that this newly cloned glucuronyltransferase is expressed in the nervous system, consistent with the selective localization of the HNK-1 carbohydrate epitope in the nervous system. Transfection of this cDNA into COS-1 cells induced the expression of the HNK-1 carbohydrate epitope on cell surfaces, and induced the morphological changes in these cells. These results indicated that this newly cloned cDNA is a second glucuronyltransferase involved in the biosynthesis of the HNK-1 carbohydrate epitope.
    Biochemical and Biophysical Research Communications 03/1999; 255(1):182-7. · 2.28 Impact Factor
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    ABSTRACT: Mannan-binding protein (MBP), a Ca2+-dependent mammalian lectin specific for mannose and N-acetylglucosamine, is an important serum component associated with innate immunity. MBP activates complement and functions as a direct opsonin on binding to mannooligosaccharide-bearing pathogens. We have found that MBP recognizes and binds specifically to oligosaccharide ligands expressed on the surfaces of a human colorectal carcinoma. Interestingly, the recombinant vaccinia virus carrying human MBP gene was demonstrated to possess a potent growth-inhibiting activity against human colorectal carcinoma cells transplanted in KSN nude mice when administered by intratumoral or subcutaneous injection. Moreover, a significant prolongation of life span of tumor-bearing mice resulted from the treatment. This effect appears to be a consequence of local production of MBP. Unexpectedly, the mutant MBP, which had essentially no complement-activating activity, was nearly as active as wild-type MBP. These results indicated that MBP has a previously undescribed cytotoxic activity, which we propose to term MBP-dependent cell-mediated cytotoxicity(MDCC). In addition, this study provides a model for the development of an effective and specific host defense factor for cancer gene therapy.
    Proceedings of the National Academy of Sciences 02/1999; 96(2):371-5. · 9.81 Impact Factor
  • K Uemura, Y Ma, H Naito, T Kawasaki, N Kawasaki
    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme 01/1999; 43(16 Suppl):2428-34.

Publication Stats

3k Citations
462.45 Total Impact Points


  • 1969–2010
    • Kyoto University
      • • Division of Pharmaceutical Sciences
      • • Graduate School of Pharmaceutical Sciences / Faculty of Pharmaceutical Sciences
      • • Department of Biophysics
      Kioto, Kyōto, Japan
  • 1998
    • Kyoto Pharmaceutical University
      Kioto, Kyōto, Japan
  • 1993–1998
    • Tokyo Metropolitan Institute of Medical Science
      Edo, Tōkyō, Japan
  • 1988–1992
    • Kyoto Sangyo University
      Kioto, Kyōto, Japan
  • 1989
    • Universiteit Utrecht
      • Division of Organic Chemistry and Catalysis
      Utrecht, Provincie Utrecht, Netherlands