| Project/Area Number |
09558088
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Functional biochemistry
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| Research Institution | Yokohama City University School of Medicine |
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Principal Investigator |
OHNO Shigeo Yokohama City Universisty School of Medicine, Department of Molecular Biology, Professor, 医学部, 教授 (10142027)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUNO Keiko Yokohama City Universisty School of Medicine, Department of Molecular Biology, A, 医学部, 助手 (90221803)
SUZUKI Atsushi Yokohama City Universisty School of Medicine, Department of Molecular Biology, L, 医学部, 講師 (00264606)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 1998: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1997: ¥7,700,000 (Direct Cost: ¥7,700,000)
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| Keywords | HB-EGF / PKC / protein kinase C / ADAM / metaloprotease / shedding / extracellular domain / membrane proteins / 細胞極性 / 上皮細胞 / 増殖 / がん |
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| Research Abstract |
Protein kinase C (PKC) has been implicated in a variety of cellular responses that include cell growth, differentiation, and apoptosis, as well as responses to a variety of physiological signals and artificial stresses. Thus, it is very important to manipulate the function of PKC in a specific manner for pharmacological manipulation of the cellular signaling cascades as well as basic research for the understanding of the intracellular signaling network. In the present study, we searched for specific binding proteins for several isotypes of the PKC family and examined the physiological meaning the the molecular interaction through a variety of methods. MDC9 is a family of membrane anchored metaloproteases. Through the interaction cloning of PKC delta, we identified MDC9 as a specific binding protein and substrate for PKCdelata. PKCdelata binds to the 25 aa sequence of the cytoplasmic domain of MDC9 and phosphorylates it efficiently. Transfection experiments using activated and trans-dominant negative mutants of PKCdelata revealed that PKC delta is involved in the TPA-induced shedding of a membrane-anchored growth factor, HB-EGF.Similar analysis using MDC9 also revealed that MDC) is also involved in the TPA-induced shedding of HB-EGF.These results suggested that PKCdelata and MDC9 are involved in the TPA-induced shedding of HB-EGF and the direct molecular interaction between PKC delta and MDC9 is involved in this process. Since the signal-induced shedding of the extra-cellular domains of a variety of proteins plays a key role in a variety of developmental and physiological processes, the present finding opened the way for the understanding of the molecular mechanism of this quite importance processes.
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