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1990 Fiscal Year Final Research Report Summary

Role of Protein Kinase C in Cellular Proliferation

Research Project

Project/Area Number 01570154
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Pathological medical chemistry
Research InstitutionFukui Medical School

Principal Investigator

HASHIMOTO Eikichi  Fukui Medical School, Associate professor, 医学部, 助教授 (20116239)

Co-Investigator(Kenkyū-buntansha) TANAKA Yukie  Fukui Medical School, Research assistant, 医学部, 教務職員 (10197486)
Project Period (FY) 1989 – 1990
KeywordsProtein kinase / Na^+ / H^+ exchanger / Down regulation / Limited proteolysis / Cell proliferation / Protease / Protein phosphorylation / 02Ca^<2+>-phospholipid- dependent protein kinase
Research Abstract

It has been proposed that protein kinase C plays important roles in cell proliferation because this enzyme is activated by diacylglycerol transiently formed by phosphatidylinositol breakdown induced by various growth factors or by tumorpromoting phorbol esters. It has also been shown that protein kinase C is subjected to limited proteolysis and down regulation of this enzyme is induced during prolonged treatment of various cells with phorbol esters. In an attempt to understand the molecular mechanism of the down regulation of protein kinase C, we analyzed the proteolytic modification of this enzyme using the rat liver plasma membrane. Under higher ionic strength than physiological level (>140 mM NaCl) and slightly alkaline pH (7.5-8.0), proteaseーactivated form of protein kinase C with Mr. 50,000 was rapidly released from the membrane. The properties of this activated enzyme were essentially the same as those of protein kinase M (corresponding to the catalytic fragment of protein kinase C) reported earlir. Based on these results, we supposed that activation of Na^+/H^+ exchanger in plasma membrane may be a trigger for inducing the down regulation of protein kinase C, because Na^+ influx and cytoplasmic alkalinization are usually observed after activation of Na^+/H^+ exchanger by various extracellular stimuli. In contrast, higher molecular weight form of protein kinase C (Mr. 80,000) was generated from membrane under lower ionic strength condion. The activity of this enzyme was stimulated 2-fold by Ca2+ and phospholipid. This partially activated kinase was converted to a Ca2+-phospholipid-independent form by further digestion with trypsin without significant change in molecullar mass. However, the physiological significance of these proteolyzed enzymes with Mr. 80,000 is not clear at this time. Further detailed analyses of down regulation of protein kinase C seems to be important for understanding the role of protein kinase C in cell proliferation.

  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] K.ハンノウ15688-15695

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hashimoto,Eikichi: "Ionic strengthーdependent interaction of rat liver casein kinase I." Biochem.Biophys.Ret.Commun.160(2). 633-637 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawata,Masahito: "Phosphorylation of smg p21ーlike GTPーbinding protein,by cyclic AMPーdependent protein kinase in a cellーfree system and in response to prostaglandin E1 in intact human platelets." J.Biol.Chem.264(26). (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hashimoto,Eikichi: "Further studies on the ionic strengthーdependent proteolytic activation of protein kinase Cin rat liver plasma membrane by endogenous trypsinーlike protease." J.Biochem.160(6). 1041-1048 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hashimoto,Eikichi: "Comparison of substrate recognition by protein kinase(type III)between rat liver cytosolic and particulate fractions." Int.J.Biochem.22(4). 405-410 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hashimoto,Eikichi: "Mechanism of proteolytic activation of rat liver protein kinase C generating Ca^<2+>ーphospholipidーindependent form with apparent molecular mass of 80,000." Int.J.Biochem.22(8). 865-871 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hashimoto,Eikichi: "Proteaseーactivated form of protein kinase C with Mr 80,000 generated from rat liver plasma membrane by trypsinーlike protease." Biochem.Int.21(5). 949-957 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hashimoto,Eikichi: "Studies on protein kinase C tightlyーbound to rat liver plasma membrane and its proteaseーactivated form." Int.J.Biochem.23(4). 395-403 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hashimoto,Eikichi: "Proteaseーactivated protein kinase C in rat liver." Int.J.Biochem.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hashimoto, E. and Yamamura, H.: "Ionic strengthーdependent interaction of rat liver case in kinase I." Biochem. Biophys. Res. Commun. 160(2). 633-637 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawata, M., Kikuchi, A., Hoshijima, M. Yamamoto, K., Hashimoto, E., Yamamura, H. and Takai, Y.: "Phosphorylation of smg p21-lide GTR-binding proteim, by cyclic AMP-dependent protein kinase in a cell-free system and in response to prostaglandin E1 in intact human platelets." J. Biol. Chem.264(26). 15688-15695 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hashimoto, E. and Yamamura, H.: "Further studies on the ionic strength-dependent proteolytic activation of protein kinase C in rat liver plasma membrane by endogenous trypsin-like protease." J. Biochem. 160(6). 1041-1048 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hashimoto, E. and Yamamura, H.: "Comparison of substrate recognition by protein kinase(type III)between rat liver cytosolic and particulate fractions." Int. J. Biochem. 22(4). 405-410 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hashimoto, E., Tanaka, Y. and Yamamura, H.: "Mechanism of proteolytic activation of rat liver protein kinase C generating Ca^<2+>-phospholipid-independent form with apparent molecular mass of 80, 000." Int. J. Biochem. 22(8). 865-871 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hashimoto, E., Takeuchi, F. and Yamamura, H.: "Proteaseーactivated form of protein kinase C with Mr 80, 000 generated from rat liver plasma membrane by trypsinーlike protease." Biochem. Int. 21(5). 949-957 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hashimoto, E., Takeuchi, F. and Yamamura, H.: "Studies on protein kinase C tightlyーbound to rat liver plasma membrane and its proteaseーactivated form." Int. J. Biochem. 23(4). 395-403 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hashimoto, E. and Yamamura, H.: "Proteaseーactivated protein kinase C in rat liver." Int. J. Biochem. (1991)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1993-08-12  

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