2004 Fiscal Year Final Research Report Summary
Analysis of the PKC-δ Signaling Pathway by Proteomics with Embryonic and Genetic Engeneering
| Project/Area Number |
15370060
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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 | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
NAKAYAMA Keiichi Kyushu university, Medical Institute of Bioregulation, Professor, 生体防御医学研究所, 教授 (80291508)
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| Co-Investigator(Kenkyū-buntansha) |
HATAKEYAMA Shigetsugu Hokkaido University, Faculty of Medicine, Professor, 大学院・医学系研究科, 教授 (70294973)
KAMURA Takumi Kyushu university, Medical Institute of Bioregulation, Associate Professor, 生体防御医学研究所, 助教授 (40333455)
NAKAYAMA Keiko Tohoku University, Faculty of Medicine, Professor, 大学院・医学系研究科, 教授 (60294972)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Embryonic and genetic engineering / Proteomics / Signal transduction / Phosphorylation / Mass analysis / Posttranslational modification / PKC-δ / Knockout mouse |
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| Research Abstract |
The accumulation of genome sequence data has facilitated the establishment of new approaches to systematic characterization of gene expression profiles at the mRNA level (transcriptome). Such strategies do not, however, necessarily provide direct information about the profile of protein expression (proteome), given that the abundance of a given mRNA does not necessarily correlate with that of the encoded protein. Furthermore, numerous characteristics of proteins, including their subcellular localization, interactions with other molecules, stability, and posttranslational modification, are amenable to study only at the protein level. Recent advances in methods for protein identification based on MS and searches of protein or DNA sequence databases have allowed high-throughput analysis of the proteome. Posttranslational modification, including phosphorylation, regulates the functions of proteins by affecting their interactions with other molecules, their enzymatic activity, or their subc
… More
ellular localization and is pivotal to the control of many cellular processes. Such modification is difficult to identify by standard proteomics approaches, however, because the modified proteins usually constitute a small proportion of all protein molecules. It is therefore necessary first to concentrate such modified proteins and to prevent contamination by highly abundant proteins. Highly sensitive MS analysis is then able to detect various types of posttranslational modification. Protein kinase C (PKC), which comprises 11 closely related isoforms, has been implicated in a wide variety of signaling mechanisms. Among PKC isotypes, PKC-δ is unique in that its overexpression results in inhibition of cell growth. We showed that mice that lack PKC-δ exhibit enlargement of peripheral lymphoid organs, expansion of the B lymphocyte population, as well as the presence of numerous germinal centers in lymphoid tissues in the absence of stimulation. We tried to develop a new approach designated "Proteomics with Embryonic and Genetic Engineering (PGEM)" to uncover the changes in PKC-δ-null mice. In this study, we established efficient and large-scale methods for phosphorylation and ubiquitylation of proteins. Furthermore, we also appled the SILAC method to quantitative analysis of the phosphoproteome. Less
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Research Products
(14 results)
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[Journal Article] Cytoplasmic ubiquitin ligase KPC regulates proteolysis of p27^<Kip1> at G1 phase.2004
Author(s)
Kamura, T., Hara, T., Matsumoto, M., Ishida, N., Okumura, F., Hatakeyama, S., Yoshida, M., Nakayama, K., Nakayama, K.I.
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Journal Title
Nature Cell Biol. 6
Pages: 1229-1235
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases.2004
Author(s)
Kamura, T., Maenaka, K., Kotoshiba, S., Matsumoto, M., Kohda, D., Conaway, R.C., Conaway, J.W., Nakayama, K.I.
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Journal Title
Genes Dev. 18
Pages: 3055-3065
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Skp2-mediated degradation of p27 regulates progression into mitosis.2004
Author(s)
Nakayama, K., Nagahama, H., Minamishima, Y.A., Miyake, S., Ishida, N., Hatakeyama, S., Kitagawa, M., lemura, S., Natsume, T., Nakayama, K.I.
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Journal Title
Dev. Cell 6
Pages: 661-672
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7.2004
Author(s)
Yada, M., Hatakeyama, S., Kamura, T., Nishiyama, M., Tsunematsu, R., Imaki, H., Ishida, N., Okumura, F., Nakayama, K., Nakayama, K.I.
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Journal Title
EMBO J. 23
Pages: 2116-2125
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Molecular clearance of ataxin-3 is regulated by a mammalian E4.2004
Author(s)
Matsumoto, M., Yada, M., Hatakeyama, S., Ishimoto, H., Tanimura, T., Tsuji, S., Kakizuka, A., Kitagawa, M., Nakayama, K.I.
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Journal Title
EMBO J. 23
Pages: 659-669
Description
「研究成果報告書概要(欧文)」より
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