| Project/Area Number |
63480126
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Kobe University |
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Principal Investigator |
KISHIMOTO Akira Kobe University, School of Medicine, Associate Professor, 医学部, 助教授 (60127363)
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| Co-Investigator(Kenkyū-buntansha) |
OGITA Kouji Kobe University, School of Medicine, Assistant, 医学部, 助手 (60204103)
KIKKAWA Ushio Kobe University, School of Medicine, Lecturer, 医学部, 講師 (40150354)
NISHIZUKA Yasutomi Kobe University, School of Medicine, Professor, 医学部, 教授 (10025546)
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥9,000,000 (Direct Cost: ¥9,000,000)
Fiscal Year 1989: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1988: ¥7,800,000 (Direct Cost: ¥7,800,000)
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| Keywords | protein kinase C / cell proliferation / cell differentiation / diacylglycerol / phorbol ester / Ca^<2+> / inositol phospholipid / signal transduction / シアシルグリセロ-ル / 蛋白質リン酸化反応 / プロテインキナーゼC / カルシウム / イノシトールリン脂質 / ホルボールエステル / 蛋白質限定分解反応 / カルパイン / ダウンレギュレーション |
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| Research Abstract |
Protein kinase C (PKC) is a multifunctional protein Ser/Thr kinase and generally accepted to be involved in a wide variety of cellular signal transduction. In this study, we have found the existence of multiple subspecies of PKC through molecular cloning and enzymological analysis. Their relative activity and individual pattern of expression and intracellular locarization in several tissues and cell types are distinctly different one another. The PKC subspecies thus far obtained from various tissues exhibit subtle differences in their mode of activation, enzymological properties, and phorbol ester-induced down-regulation.
In addition, the expressions of PKC subspecies are differently regulated during the differentiation of HL-60 cell toward granulocyte. Thus, it is strongly suggested that the members of PKC family each show distinctly different preference for substrate proteins that are located in specific intracellular comportments of the cell types in which they are expressed. Analysis of the activation of T-lymphocyte through PKC activation using phorbol esters or membrane-permeable diacylglycerols indicates a dual action of PKC, modulation of membrane receptor and regulation of gene expression. Short term PKC activation, which may be induced by the breakdown of inositol phospholipid, provides the down-regulation of TCR-CD3 complex on the surface of lymphocyte. On the other hand, sustained PKC activation is necessary to enhance the expression of IL-2 receptor eventually leading to cell proliferation.
There appear to be several additional routes, other than the hydrolysis of inositol phospholipid, to provide the diacylglycerol that is needed for prolonged enzyme activation. This novel mechanisms leading to PKC activation as well as functional specificities of PKC subspecies remain to be explored to elucidate roles of PKC in the regulation of gene expression and growth control.
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