KAI Masahiro

写真a

Affiliation

School of Medicine, Department of Molecular Biology

Job title

Lecturer
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Education 【 display / non-display 】

  • 　
    -
    1993

    Tokyo Institute of Technology  

  • 　
    -
    1993

    Tokyo Institute of Technology  

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Degree 【 display / non-display 】

  • Ph.D.

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Professional Memberships 【 display / non-display 】

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    Japanese Biochemical Society

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    日本生化学会

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Affiliation 【 display / non-display 】

  • Sapporo Medical University   School of Medicine, Biochemistry   Instructor  

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Research Interests 【 display / non-display 】

  • 生化学

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Misc 【 display / non-display 】

  • The plasma membrane translocation of diacylglycerol kinase delta 1 is negatively regulated by conventional protein kinase C-dependent phosphorylation at Ser-22 and Ser-26 within the pleckstrin homology domain

    S Imai, M Kai, K Yamada, H Kanoh, F Sakane

    BIOCHEMICAL JOURNAL ( PORTLAND PRESS )  382 ( 3 ) 957 - 966  2004.09

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    DGK (diacylglycerol kinase) regulates the concentration of two bioactive lipids, diacylglycerol and phosphatidic acid. DGKdelta1 or its PH (pleckstrin homology) domain alone has been shown to be translocated to the plasma membrane from the cytoplasm in PMA-treated cells. In the present study, we identified Ser-22 and Ser-26 within the PH domain as the PMA- and epidermal-growth-factor-dependent phosphorylation sites of DGKdelta1. Experiments in vitro and with intact cells suggested that the cPKC (conventional protein kinase C) phosphorylated these Ser residues directly. Puzzlingly, alanine/asparagine mutants at Ser-22 and Ser-26 of DGKdelta1 and its PH domain are still persistently translocated by PMA treatment, suggesting that the PH domain phosphorylation is not responsible for the enzyme translocation and that the translocation was caused by a PMA-dependent, but cPKC-independent, process yet to be identified. Interestingly, the aspartate mutation, which mimics phosphoserine, at Ser-22 or Ser-26, inhibited the translocation of full-length DGKdelta1 and the PH domain markedly, suggesting that the phosphorylation regulates negatively the enzyme translocation. Our results provide evidence of the phosphorylation of the DGKdelta1 PH domain by cPKC, and suggest that the phosphorylation is involved in the control of subcellular localization of DGKdelta1.

    DOI PubMed CiNii

  • Diacylglycerol kinase gamma serves as an upstream suppressor of Rac1 and lamellipodium formation

    S Tsushima, M Kai, K Yamada, S Imai, K Houkin, H Kanoh, F Sakane

    JOURNAL OF BIOLOGICAL CHEMISTRY ( AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC )  279 ( 27 ) 28603 - 28613  2004.07

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    Nine diacylglycerol kinase (DGK) isozymes have been identified. However, our knowledge of their individual functions is still limited. Here, we demonstrate the role of DGKgamma in regulating Rac1-governed cell morphology. We found that the expression of kinase-dead DGKgamma, which acts as a dominant-negative mutant, and inhibition of endogenous DGKgamma activity with R59949 induced lamellipodium and membrane ruffle formation in NIH3T3 fibroblasts in the absence of growth factor stimulation. Reciprocally, lamellipodium formation induced by platelet-derived growth factor was significantly inhibited upon expression of constitutively active DGKgamma. Moreover, the constitutively active DGKgamma mutant suppressed integrin-mediated cell spreading. These effects are isoform-specific because, in the same experiments, none of the corresponding mutants of DGKalpha and DGKbeta, closely related isoforms, affected cell morphology. These results suggest that DGKgamma specifically participates in the Rac1-mediated signaling pathway leading to cytoskeletal reorganization. In support of this, DGKgamma co-localized with dominant-active Rac1 especially in lamellipodia. Moreover, we found that endogenous DGKgamma was physically associated with cellular Rac1. Dominant-negative Rac1 expression blocked the lamellipodium formation induced by kinase-dead DGKgamma, indicating that DGKgamma acts upstream of Rac1. This model is supported by studies demonstrating that kinase-dead DGKgamma selectively activated Rac1, but not Cdc42. Taken together, these results strongly suggest that DGKgamma functions through its catalytic action as an upstream suppressor of Rac1 and, consequently, lamellipodium/ruffle formation.

    DOI PubMed CiNii

  • Heparin-binding EGF-like growth factor is a promising target for ovarian cancer therapy.

    Cancer Res   64   5720 - 7  2004

    DOI

  • Differential localization of lipid phosphate phosphatases 1 and 3 to cell surface subdomains in polarized MDCK cells

    YJ Jia, M Kai, Wada, I, F Sakane, H Kanoh

    FEBS LETTERS ( ELSEVIER SCIENCE BV )  552 ( 2-3 ) 240 - 246  2003.09

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    Lipid phosphate phosphatases (LPPs) are integral membrane proteins with six transmembrane domains that act as ecto-enzymes dephosphorylating a variety of extracellular lipid phosphates. Using polarized MDCK cells stably expressing human LPP1 and LPP3, we found that LPP1 was located exclusively at the apical surface whereas LPP3 was distributed mostly in the basolateral subdomain. We identified a novel apical sorting signal at the N-terminus of LPP1 composed of F(2)DKTRL(7). In the case of LPP3, a dityrosine motif present in the second cytoplasmic portion was identified as basolateral targeting signal. Our work shows that LPP1 and LPP3 are equipped with distinct sorting signals that cause them to differentially localize to the apical vs. the basolateral subdomain, respectively. (C) 2003 Published by Elsevier B.V. All rights reserved.

    DOI PubMed CiNii

  • Cell surface activities of the human type 2b phosphatidic acid phosphatase.

    J Biochem (Tokyo)   127   645 - 51  2000

    DOI

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Research Projects 【 display / non-display 】

  • リン脂質代謝酵素の機能解析

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