Mechanism of T cell growth-signal transduction and its abnormality

T细胞生长信号转导机制及其异常

• 批准号: 03670172
• 负责人: NAMBA Yuziro
• 金额: $ 1.22万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670172/
• 关键词: protein phosphorylation; T lymphocyte; 1-plastin; IL 2; actin-binding protein; calcium-binding protein; monoclonal antibody; microfilament; シグナル伝達; リンパ球の増殖; カルシウム

65-kilodalton protein has been characterized as an interleukin 2-stimulated phosphoprotein in human T cells. We determined the complete primary structure of p65 based on the cDNA isolated from a human T lymphocyte (KUT-2) cDNA library. Analysis of p65 sequence indicated that p65 is multidomain molecule involving at least three intriguing domains; two putative calcium-binding sited along the N- terminal 80 amino acid residues; a putative calmodulin-binding site following the calcium binding region; and two tandem repeats of putative actin-binding domains in its middle and C-terminal parts, each containing approximately 240 residues. This domain structure closely resembles a chicken intestinal microvilli protein, fimbrin, that bundles actin filaments. It was observed that unphosphorylated L-plastin isolated from human T cells bundles F-actin just as fimbrin does. L-plastin acted on T cell beta-actin, but hardly acted on muscle alpha-actin or chicken gizzard gamma-actin, whereas fimbrin bundles alpha-actin. Unlike fimbrin, L-plastin's actin-bundliung action was strictly calcium-dependent: the bundles were formed at pCa 7, but not at pCa 6. Under suitable conditions, approximately one molecule of L-plastin bound to 8 molecules of actin monomer in the actin filament.

65 kilodalton蛋白已被描述为人白细胞介素2刺激的人类T细胞中的磷酸蛋白。我们基于从人T淋巴细胞（KUT-2）cDNA文库中分离的cDNA确定了p65的完整一级结构。对p65序列的分析表明，p65是涉及至少三个有趣域的多域分子。沿着N-末端80氨基酸残基的两个假定的钙结合；钙结合区域之后的推定钙调蛋白结合位点；以及在其中间和C末端部分的两个推定肌动蛋白结合域的串联重复序列，每个均包含大约240个残基。该结构结构与鸡肠道微绒毛蛋白（纤维蛋白）非常相似，该蛋白束束肌动蛋白丝。据观察，从人类T细胞中分离出的未磷酸化的L-普拉斯汀就像Fimbrin一样。 L-帕斯汀作用于T细胞β-肌动蛋白，但几乎没有作用于肌肉α-肌动蛋白或鸡gizzardγ-肌动蛋白，而fimbrin捆绑蛋白α-肌动蛋白。与纤维蛋白不同，L-普拉斯汀的肌动蛋白 - 串联作用严格取决于钙的依赖性：束在PCA 7处形成，但在PCA 6中不是形成。在合适的条件下，大约一个L-铂分子结合到肌动蛋白丝状中的肌动蛋白单体的8个分子。

项目成果

Namba,Y.,Ito,M.,ZU,Y.,Shigesada,K.& Maruyama,K.: "Human T cell 1-Plastin bundles actin filaments in a calcium dependent manner." J.Biochemistry. 112. 503-507 (1992)

难波 Y.、伊藤 M.、ZU,Y.、重定 K.

Kondo,S.,Miyatake,S.,Kikuchi,H.,Shamoto,M.〓 Namba,Y.: "Human glioma-specific antigens detected by monoclonal antibodies." Neurosurgery. 30. 506-511 (1992)

Kondo, S.、Miyatake, S.、Kikuchi, H.、Shamoto, M.〓 Namba, Y.：“通过单克隆抗体检测的人类神经胶质瘤特异性抗原。” 30. 506-511 (1992)

Kondo,S.,Miyatake,S.,Kikuchi,H.,Oda,Y. & Namba,Y.: "Mechanism of interferon gamma-induced protection of human gliosarcoma cells from lymphokine-activated killer lysis." Neurosurgery. 31. 534-540 (1992)

近藤S.，宫武S.，菊池H.，小田Y.

Haga,S.,Shigesada,K.,Nambo,Y.,Tanaka,H. & Hilgers,J.: "Polyclonal and monoclonal antibodies monospecific to MMTV LTR orf protein produced in E. coli." Cancer Letter. 65. 201-207 (1992)

Haga,S.,Shigesada,K.,Nambo,Y.,Tanaka,H.

Kondo,S.,Miyatake,S.,Kikuchi,H.& Namba,Y.: "Human gliomaーspecific antigens detected by monoclonal antibodies" Neurosurgery. (1992)

Kondo, S.、Miyatake, S.、Kikuchi, H. 和 Namba, Y.：“单克隆抗体检测到的人类神经胶质瘤特异性抗原”神经外科 (1992)。