cDNA cloning of the recepters for the members of TGFbeta superfamily

TGFbeta超家族成员受体的cDNA克隆

• 批准号: 05671566
• 负责人: KATO Hirohisa
• 金额: $ 1.41万
• 依托单位: National Institute of Health of Japan
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671566/
• 关键词: TGFbeta; microfilament; reverse transformation; TGF-beta; TGF-betaスーパーファミリー; TGF-betaリセプター

The factors, which are members of TGFbeta superfamily, especially TGFbeta are thought to be playing key roples in the regulation of cellular replication and defferentiation, wound healing, remodeling of the bone and hoematopoiesis. Among them, inhibitory effect of TGFbeta on the cellular growth has been studied by many investigators especially from the viewpoint of cancer research. The cDNA cloning of the receptors of these factors have been tried in order to analyze the mechanism of these factors. We cloned 2-3 clones using the highly homologous region of the type 2 recepter of TGFbeta. We are going to analyze these clones futher.On the other hand, it was found that TGF beta alter the cellular morphology of the human lung carcinoma cell line A549 from epithelial-like cells to the fibroblastic spindle shaped flat cells. Although this fact is already reported, it was also found that TGF beta can converted the morphology and concomitantly suppress the transformed phenotype of the cells, namely growth ability in the soft agar and in monolayr culture, saturation density in monolayr culture. And it was noticed that the alteration in morphology is related to the loss of the transformed phenotype.When CHO-K1 cells are exposed to the derivatives of cAMP,it was also observed that transformed phenotype is strongly suppressed and concomitantly cell morphology is altered in a similar way. This phenomenon is called reverse transformation or redifferentiation. It is proposed by us that the effect caused by TGF beta is closely related to the reverse transformation. Further, we are going to analyze the effects caused by other members of this superfamily, namely bone morphogenetic protein, activin A.

这些因子是转化生长因子β超家族的成员，尤其是转化生长因子β，被认为在调节细胞复制和分化、伤口愈合、骨重塑和造血方面发挥着关键作用。其中，转化生长因子β对细胞生长的抑制作用已被许多研究者研究，特别是从肿瘤研究的角度。为了分析这些因子的作用机制，我们尝试了这些因子受体的克隆。我们利用转化生长因子β2型受体的高度同源区域克隆了2-3个克隆。我们将对这些克隆进行进一步的分析。另一方面，我们发现转化生长因子β使人肺癌细胞系A549的细胞形态从上皮样细胞转变为成纤维细胞梭形的扁平细胞。虽然这一事实已有报道，但也发现转化生长因子β可以改变细胞的形态，并伴随着抑制转化的表型，即在软琼脂和单层培养中的生长能力，在单层培养中的饱和密度。当CHO-K1细胞暴露于cAMP的衍生物时，也观察到转化表型受到强烈抑制，并伴随着类似的细胞形态改变。这种现象被称为反向转化或再分化。我们提出，转化生长因子β的作用与逆转化密切相关。此外，我们将分析这个超家族的其他成员，即骨形态发生蛋白，激活素A所造成的影响。

项目成果

太田、加藤、広田、今井、石川、大和、湊: "Immunochemical analysis and localization of a cell wall antigen of Streptococcus rattus with a specific monoclonal antibody." Zentralblat fur Bakteriologie International Journal of Medical Microbiology. (in press).

Ota、Kato、Hirota、Imai、Ishikawa、Yamato、Minato：“用特定单克隆抗体对鼠链球菌细胞壁抗原进行免疫化学分析和定位。”Zentralblat Fur Bakteriologie International Journal of Medical Microbiology（正在出版）。

山田、加藤、神田,藤井-栗山、宇多小路,伊藤: "Sequence homology of Chinese hamster metallothionein genes I and II to those of the mouse and rat,and their amplification in Cd-resistant cells." Biochimica et Biophysica Acta. 1219. 581-591 (1994)

Yamada、Kato、Kanda、Fujii-Kuriyama、Utakoji、Ito：“中国仓鼠金属硫蛋白基因 I 和 II 与小鼠和大鼠的序列同源性，以及它们在 Cd 抗性细胞中的扩增。” 581-591 (1994)

太田、加藤、広田 井上、友武,内山、湊: "Immunochemical study of polysaccharide antigen in Streptococcus downei with a cross-reactive monoclonal antibody." FEMS Immunology and Medical Microbiology.8. 213-218 (1994)

Ota、Kato、Hirota Inoue、Tomotake、Uchiyama、Minato：“用交叉反应单克隆抗体对唐氏链球菌中的多糖抗原进行免疫化学研究。”FEMS 免疫学和医学微生物学。8 (1994)。

多田、加藤: "Supression of transformed phenotype by transforming growth factor β." 42nd Annual Meeting,Japanese Association for Dental Research.(国際歯科研究学会日本部会)J.Den.Res.(in press).

Tada，Kato：“通过转化生长因子 β 抑制转化表型。”第 42 届日本牙科研究协会年会（J.Den.Res）。

太田、加藤、広田、今井、石川、大和,湊: "Immunochemical analysis and localization of a cell wall antigen of Streptococcus rattus with a specific monoclonal antibody." Zentralblat fur Bakteriologie International Journal of Medical Microbiology. (in press).

Ota、Kato、Hirota、Imai、Ishikawa、Yamato、Minato：“用特定单克隆抗体对鼠链球菌细胞壁抗原进行免疫化学分析和定位。”Zentralblat Fur Bakteriologie International Journal of Medical Microbiology（正在出版）。