1990 Fiscal Year Final Research Report Summary
Mechanism of T Cell Proliferation : Intracellular Protein of IL 2 Signal Transduction
| Project/Area Number |
01570191
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Kyoto University |
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Principal Investigator |
NAMBA Yuziro Institute for Virus Research, Kyoto Univ. Department of Cell Biology, Associate Prof., ウイルス研究所, 助教授 (50027322)
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| Project Period (FY) |
1989 – 1990
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| Keywords | Protein Phosphorylation / 1-Plastin / Actin binding protein / IL 2 |
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| Research Abstract |
We have characterized a 65-kilodalton protein (p65) as an interleukin 2-stimulated phosphoprotein in human T cells and showed that three endopeptide produced by digestion with lysylendopeptidase of the purified p65 had aminoacid sequences identical with those present in 1-plastin. We have determined the complete primary structure of p65 based on the cDNA isolated from a human T lymphocyte (KUT-2) cDNA library. Analysis of p65 sequences and the amino acid composition of cleaved p65 N-terminal peptide indicated that the deduced p65 amino acid sequence exactly coincides with that of 1-plastin over the C-terminal 580 residues and has a 57-residue extention at the N-terminus to 1-plastin. Computer-assisted structural analysis revealed that p65 is a multidomain molecule involving at least three intriguing functional domains : two putative calcium-binding regions ; and two tandem repeats of putative actin- binding domains in its middle and C-terminal parts, each containing approximately 240 amino acid residues. These results suggest that p65 belong to actin-binding proteins.
The serine residue of p65 which is phosphorylated by IL 2 stimulation exists in the first EF-hand Ca-binding site, suggesting that the phosphorylation of this serine residue might change the calcium dependency of p65.
The mutant gene was constructed in which this serine residue being exchanged to glycine residue. This mutant gene was inserted into the vector which contain metallothionein promotor and transfected to UW-4 cells. By the expression of this mutant protein with zinc sulfate, the I1 2-induced proliferation was severely inhibited suggesting that the phosphorylation of this protein participate in the transduction of IL 2 growth signal.
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[Publications] Miyatake,S.,Kikuchi,H.,Oda,Y.,Nishioka,T.,Takahashi,J.,Kondon,S.and Namba,Y.:"Decreased susceptibility of lined human glioma cells to lymphokineーactivated killer cell cytolysis by rーinterferon treatment." Cancer Research. 50. 596-600 (1990)
Description
「研究成果報告書概要(和文)」より
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[Publications] Miyatake,S.,Nishihara,K.,Kikuchi,H.,Yamashita,J.,Namba,Y.and Watanabe,Y.:"Efficient tumor suppression by interferonーr geneーtransferred gliomaーspecific murine cytotoxic Tーlymphocytes." J.Natl.Cancer Inst.,. 82. 217-220 (1990)
Description
「研究成果報告書概要(和文)」より
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[Publications] Iwahashi,M.,Hanada,S.,Kanaitsuka,T.,Utsunomiya,A.,Ishibashi,K.& Namba,Y.:"cーfos gene expression in mononuclear cells of ATL patients and HTLVー1 healthy carriers." Acta Hematologica Japonica. 53. 942-950 (1990)
Description
「研究成果報告書概要(和文)」より
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[Publications] Zu,Y.,Shigesada,K.,Nishida,E.,Kubota,I.,Kohno,M.,Hanaoka,M.& Namba,T.:"65ーKilodalton protein phosphorylated by IL 2ーstimulation bears two putative actin binding sites and two calcium binding sites." Biochemistry. 29. 8319-8324 (1990)
Description
「研究成果報告書概要(和文)」より
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[Publications] Kondoh,S.,Miyatake,S.,Kikuchi,H.,Oda,Y.,Iwasaki,H.,Aoki,T.& Namba,Y.:"Mechanism of IFNーrーinduced protection of human gliosarcoma cells from lymphokineーactivated killer (LAK) lysis:Division of LAK cells from NKー and Tーlike cells" Cancer Research. (1991)
Description
「研究成果報告書概要(和文)」より
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[Publications] Zu,Y.,Kohno,M.,Kubota,I.,Nishida,E.,Hanaoka,M.and Namba,Y.:"Charcterization of interleukin 2 stimulated 65ーkilodalton phosphoprotein in human T cells." Biochemistry. 29. 1055-1062 (1990)
Description
「研究成果報告書概要(和文)」より
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[Publications] Miyatake, S., Kikuchi, H., Oda, Y., Nishioka, T., Takahashi, J., Kondoh, S. and Namba, Y.: "Decreased susceptibility of lined human glioma cells to lymphokine-activated killer cell cytolysis by r-interferon treatment." Cancer Research. 50. 596-600 (1990)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Miyatake, S., Nishihara, K., Kikuchi, H., Yamashita, J., Namba, Y. and Watanabe, Y.: "Efficient tumor suppression by interferon-r gene-transferred glioma-specific murine cytotoxic T-lymphocytes." J. Natl. Cancer Inst.82. 217-220 (1990)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Iwahashi, M., Hanada, S., Kanaitsuka, T., Utsunomiya, A., Ishibashi, K. and Namba, Y.: "C-Fos gene expression in mononuclear cells of ATL patients and HTLV-1 healthy carriers." Acta Hematol. Jpn.53. 942-950 (1990)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Zu, Y., Kohno, M., Kubota, I., Nishida, E., Hanaoka, M. and Namba, Y.: "Characterization of interleukin 2 stimulated 65-kilodalton phosphoprotein in human T cells." Biochemistry. 29. 1055-1062 (1990)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Zu, Y., Shigesada, K., Nishida, E., Kubota, I., Kohno, M., Hanaoka, M. and Namba, Y.: "65-kilodalton protein phosphorylated by IL 2-stimulation bears two putative actin binding sites and two calcium binding sites." Biochemistry. 29. 8319-8324 (1990)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Kondoh, S., Miyatake, S., Kikuchi, H., Oda, Y., Iwasaki, H., Aoki, T and Namba, Y.: "Mechanism of IFN-r-induced protection of human gliosarcoma cells from lymphokine-activated killer (LAK) lysis : Division of LAK cells from NK- and T-like cells." Cancer Research.
Description
「研究成果報告書概要(欧文)」より
