2004 Fiscal Year Final Research Report Summary
Investigation of Tec family of protein-tyrosine kinases in hematopoiesis and hematological disorders.
Project/Area Number |
15591023
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Hematology
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Research Institution | Jichi Medical School |
Principal Investigator |
YAMASHITA Yoshihiro Jichi Medical School, Department of Medicine, Research Associate, 医学部, 助手 (10326861)
|
Project Period (FY) |
2003 – 2004
|
Keywords | Sak kinase / Tec kinsase / tyrosine phosphorylation / PEST sequence |
Research Abstract |
The murine sak gene encodes a putative serine-threonine kinase which is homologous to the members of the Plk/Polo family. Although Sak protein is presumed to be involved in cell growth mechanism, efforts have failed to demonstrate its kinase activity. Little has been, therefore, elucidated how Sak is regulated and how Sak contributes to cell proliferation. Tec is a cytoplasmic protein-tyrosine kinase(PTK) which becomes activated by the stimulation of cytokine receptors, lymphocyte surface antigens, heterotrimeric G protein-linked receptors, and integrins. To clarify the in vivo function of Tec, we have tried to isolate the second messengers of Tec by using the yeast two-hybrid screening. One of such Tec-binding proteins turned out to be Sak. In human kidney 293 cells, Sak became tyrosine-phosphorylated by Tec, and the serine-threonine kinase activity of Sak was detected only under the presence of Tec, suggesting Sak to be an effector molecule of Tec. In addition, Tec activity efficiently protects Sak from the "PEST" sequence-dependent proteolysis. Internal deletion of the PEST sequences led to the stabilization of Sak proteins, and expression of these mutants acted suppressive to cell growth. Our data collectively supports a novel role of Sak acting in the PTK-mediated signaling pathway.
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Research Products
(12 results)
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[Journal Article] Signal transducers and activators of transcription 3 augments the transcriptional activity of CCAAT/enhancer-binding protein alpha in granulocyte colony-stimulating factor signaling pathway2005
Author(s)
Numata, A., Shimoda, K., Kamezaki, K., Haro, T., Kakumitsu, H., Shide, K., Kato, K., Miyamoto, T., Yamashita, Y., Oshima, Y., Nakajima, H., Iwama, A., Aoki, K., Takase, K., Gondo, H., Mano, H., Harada, M.
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Journal Title
J Biol Chem (Epub 12005 Jan 12621) 280
Pages: 12621-12629
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The Tyr-kinase inhibitor AG879, that blocks the ETK-PAK1 interaction, suppresses the RAS-induced PAK1 activation and malignant transformation2004
Author(s)
He, H., Hirokawa, Y., Gazit, A., Yamashita, Y., Mano, H., Kawakami, Y., Kawakami, Hsieh, C.Y., Kung, H.J., Lessene, G., Baell, J., Levitzki, A., Maruta, H.
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Journal Title
Cancer Biol Ther (Epub 2004 Jan 2029) 3
Pages: 96-101
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] High-throughput screening of genome fragments bound to differentially acetylated histones2004
Author(s)
Kaneda, R., Toyota, M., Yamashita, Y., Koinuma, K., Choi, Y.L., Ota, J., Kisanuki, H., Ishikawa, M., Takada, S., Shimada, K., Mano, H.
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Journal Title
Genes Cells 9
Pages: 1167-1174
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] DNA microarray analysis of dysplastic morphology associated with acute myeloid leukemia2004
Author(s)
Tsutsumi, C., Ueda, M., Miyazaki, Y., Yamashita, Y., Choi, Y.L., Ota, J., Kaneda, R., Koinuma, K., Fujiwara, S., Kisanuki, H., Ishikawa, M., Ozawa, K., Tomonaga, M., Mano, H.
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Journal Title
Exp Hematol 32
Pages: 828-835
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Reprogramming of human postmitotic neutrophils into macrophages by growth factors2004
Author(s)
Araki, H., Katayama, N., Yamashita, Y., Mano, H., Fujieda, A., Usui, E., Mitani, H., Ohishi, K., Nishii, K., Masuya, M., Minami, N., Nobori, T., Shiku, H.
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Journal Title
Blood (Epub 2003 Dec 2930) 103
Pages: 2973-2980
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] DNA microarray analysis of natural killer cell-type lymphoproliferative disease of granular lymphocytes with purified CD3-CD56+ fractions2004
Author(s)
Choi, Y.L., Makishima, H., Ohashi, J., Yamashita, Y., Ohki, R., Koinuma, K., Ota, J., Isobe, Y., Ishida, F., Oshimi, K., Mano, H.
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Journal Title
Leukemia 18
Pages: 556-565
Description
「研究成果報告書概要(欧文)」より