1989 Fiscal Year Annual Research Report

Protein Kinase Cの分子多様性とその構造、機能の研究

Research Project

Project/Area Number	63480126
Research Institution	Kobe University
Principal Investigator	岸本明神戸大学, 医学部, 助教授 (60127363)
Co-Investigator(Kenkyū-buntansha)	荻田浩司神戸大学, 医学部, 助手 (60204103) 西塚泰美神戸大学, 医学部, 教授 (10025546)
Keywords	プロテインキナ-ゼC / 細胞増殖 / 細胞分化 / シアシルグリセロ-ル / ホルボ-ルエステル / カルシウムイオン / 細胞内情報伝達 / イノシト-ルリン脂質
Research Abstract	プロテインキナ-ゼC(PKC)は、外界情報の受容伝達の主軸として、多岐の生理活性物質による細胞機能の調節に深く関与していることが確実視されている。昨年度はPKCを介する情報伝達機構の化学的基盤の解明に焦点をあてた解析を実施し、cDNAの解析によるPKCの構造解析と酵素化学的解析からPKCの多様性が情報伝達機構を多彩なものとしていることを明らかにし得た。本年度は最終年度であることにかんがみ、細胞の活性化や分化誘導におけるPKC分子種の動態の解析に焦点を当てた。retinoic acidは白血病細胞株HL-60の顆粒球様細胞への分化を促進する。この時retinoic acidはPKCを直接活性化するのではなく、PKC分子種に固有の発現調節を行っている。HL-60細胞では、αとβのPKCに加えて今一つ未同定のPKCが存在する。retinoic acid刺激によってβのPKCが著名に増加し、αともう一つのPKCは減少している。これは腫瘍化した細胞にα-PKCが多いという結果と一致している。γ-PKCが中枢神経系にのみ発現されているということとあわせて、各PKC分子種が細胞機能に応じて独立して発現調節を受けていることを強く示唆するものである。膜透過性ジアシルグリセロ-ル(DC_8)は細胞内PKCの活性化を引き起こし、種々の実験系に有効利用されている。リンパ球ではDC_8の短期間の刺激では細胞の応答が見られず、反復して刺激を持続させることがIL-2受容体の発現等の細胞応答に必須であることが判明した。これらの結果は、従来のイノシト-ルリン脂質の代謝回転による短期間のジアシルグリセロ-ルの産生に対する応答のみでなく、長期間のジアシルグリセロ-ル産生機序の解明とその間のPKC分子種に特異的な活性化や動態の把握、またPKC分子種に固有の発現調節といった新しい観点を与えるものであり、今後の生理機能の解析へつなげることができた。

Research Products
(16 results)

All Other

All Publications (16 results)

[Publications] Kishimoto,A.: "Limited proteolysis of protein kinase C subspecies by calcium-dependent neutral protease(calpain)." J.Biol.Chem.264. 4088-4092 (1989)
[Publications] Berry,N.: "Human T cell activation by phorbol esters and diacylglycerol analogues." J.Immunol.143. 1407-1413 (1989)
[Publications] Shearman,M.S.: "Selective activation of the γ-subspecies of protein kinase C from bovine cerebellum by arachidonic acid and its lipoxygenase metabolites." FEBS Lett.243. 177-182 (1989)
[Publications] Bignon,E.: "Modes of inhibition of protein kinase C by triphenylacrylonitrile antiestrogens." Biochem.Biophys.Res.Commun.163. 1377-1383 (1989)
[Publications] Kikkawa,U.: "The protein kinase C family:heterogeneity and its implications." Ann.Rev.Biochem.58. 31-44 (1989)
[Publications] Ogita,K.: "The structure and function of multispecies of protein kinase C." Adv.Prostaglandin Thrombozane Leukotriene Res.19. 49-56 (1989)
[Publications] Kikkawa,U.: "The heterogeneity of protein kinase C and its implications for neuronal cell regulation." Brain Signal Transduction and Memory. 21-32 (1989)
[Publications] Kishimoto,A.: "The protein kinase C family in the brain:heterogeneity and its implications." Ann.N.Y.Acad.Sci.568. (1990)
[Publications] Berry,N.: "Activation of resting human T cells requires prolonged stimulation of protein kinase C." Proc.Natl.Acad.Sci.USA. (1990)
[Publications] Ito,A.: "Immunocytochemical localization of α subspecies of protein kinase C in rat brain." Proc.Natl.Acad.Sci.USA. (1990)
[Publications] Hashimoto,K.: "Protein kinase C during differentiation of human promyelocytic leukemia cell line HL-60." FEBS Lett.(1990)
[Publications] Yasuda,I.: "A synthetic peptide substrate for selective assay of protein kinase C." Biochem.Biophys.Res.Commun.166. 1220-1227 (1990)
[Publications] Hashimoto,K.: "Calpains and regulation of protein kinase C." The Calcium-dependent Proteolytic System of Mammalian Cells. (1990)
[Publications] Ogita,K.: "The heterogeneity of protein kinase C in signal transduction cascade." Adv.Second Messenger Phosphoprotein Res.(1990)
[Publications] Ishii,S.: "Structure and function of the protein CRE-BP1:heterogeneity of the protein that binds to the cAMP-responsive element." Adv.Second Messenger Phosphoprotein Res.(1990)
[Publications] Kishimoto,A.: "Limited proteolysis of protein kinase C by calpain,its possible implication." Adv.Second Messenger Phosphoprotein Res.(1990)

1989 Fiscal Year Annual Research Report

Protein Kinase Cの分子多様性とその構造、機能の研究

Principal Investigator

岸本 明 神戸大学, 医学部, 助教授 (60127363)

Research Products

[Publications] Kishimoto,A.: "Limited proteolysis of protein kinase C subspecies by calcium-dependent neutral protease(calpain)." J.Biol.Chem.264. 4088-4092 (1989)

[Publications] Berry,N.: "Human T cell activation by phorbol esters and diacylglycerol analogues." J.Immunol.143. 1407-1413 (1989)

[Publications] Shearman,M.S.: "Selective activation of the γ-subspecies of protein kinase C from bovine cerebellum by arachidonic acid and its lipoxygenase metabolites." FEBS Lett.243. 177-182 (1989)

[Publications] Bignon,E.: "Modes of inhibition of protein kinase C by triphenylacrylonitrile antiestrogens." Biochem.Biophys.Res.Commun.163. 1377-1383 (1989)

[Publications] Kikkawa,U.: "The protein kinase C family:heterogeneity and its implications." Ann.Rev.Biochem.58. 31-44 (1989)

[Publications] Ogita,K.: "The structure and function of multispecies of protein kinase C." Adv.Prostaglandin Thrombozane Leukotriene Res.19. 49-56 (1989)

[Publications] Kikkawa,U.: "The heterogeneity of protein kinase C and its implications for neuronal cell regulation." Brain Signal Transduction and Memory. 21-32 (1989)

[Publications] Kishimoto,A.: "The protein kinase C family in the brain:heterogeneity and its implications." Ann.N.Y.Acad.Sci.568. (1990)

[Publications] Berry,N.: "Activation of resting human T cells requires prolonged stimulation of protein kinase C." Proc.Natl.Acad.Sci.USA. (1990)

[Publications] Ito,A.: "Immunocytochemical localization of α subspecies of protein kinase C in rat brain." Proc.Natl.Acad.Sci.USA. (1990)

[Publications] Hashimoto,K.: "Protein kinase C during differentiation of human promyelocytic leukemia cell line HL-60." FEBS Lett.(1990)

[Publications] Yasuda,I.: "A synthetic peptide substrate for selective assay of protein kinase C." Biochem.Biophys.Res.Commun.166. 1220-1227 (1990)

[Publications] Hashimoto,K.: "Calpains and regulation of protein kinase C." The Calcium-dependent Proteolytic System of Mammalian Cells. (1990)

[Publications] Ogita,K.: "The heterogeneity of protein kinase C in signal transduction cascade." Adv.Second Messenger Phosphoprotein Res.(1990)

[Publications] Ishii,S.: "Structure and function of the protein CRE-BP1:heterogeneity of the protein that binds to the cAMP-responsive element." Adv.Second Messenger Phosphoprotein Res.(1990)

[Publications] Kishimoto,A.: "Limited proteolysis of protein kinase C by calpain,its possible implication." Adv.Second Messenger Phosphoprotein Res.(1990)

岸本明神戸大学, 医学部, 助教授 (60127363)