GROWTH-INHIBITION BY TRANSFORMING GROWTH FACTOR-BETA(TGF-BETA) TYPE-I IS RESTORED IN TGF-BETA-RESISTANT HEPATOMA-CELLS AFTER EXPRESSION OF TGF-BETA RECEPTOR TYPE-II CDNA

GROWTH-INHIBITION BY TRANSFORMING GROWTH FACTOR-BETA(TGF-BETA) TYPE-I IS RESTORED IN TGF-BETA-RESISTANT HEPATOMA-CELLS AFTER EXPRESSION OF TGF-BETA RECEPTOR TYPE-II CDNA
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DOI:
10.1073/pnas.90.11.5359
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发表时间:
1993-06-01
影响因子:
11.1
通讯作者:
CARR, BI
CARR, BI
中科院分区:
综合性期刊1区
文献类型:
--
作者:
INAGAKI, M;MOUSTAKAS, A;CARR, BI

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TGF-β1 有效抑制人肝癌 Hep 3B 细胞的生长(ID50 = 0.2 ng/ml,8 pM)。衍生出一种突变细胞系,该细胞系的生长不受 5 ng/ml (200 pM) TGF-β1 的抑制,并且缺乏 II 型 TGF-β 受体 (TGF-betaRII) 基因。将克隆的人 TGF-betaRII cDNA 转染到该突变细胞系中,可恢复受体表达以及 TGF-beta1 对生长的抑制。在用 TGF-βRII cDNA 稳定转染的野生型和突变细胞中,TGF-βRII 在配体存在下与 I 型 TGF-β 受体共免疫沉淀。这些实验为 TGF-βRII 在 TGF-β 对生长的抑制作用中的作用提供了直接证据,并表明 TGF-βRII 通过与 I 型 TGF-β 受体的异聚表面复合物发挥作用。
The growth of human hepatoma Hep 3B cells is potently inhibited by TGF-beta1 (ID50 = 0.2 ng/ml, 8 pM). A mutant cell line was derived that was not inhibited in growth by TGF-beta1 at 5 ng/ml (200 pM) and that lacked TGF-beta receptor type II (TGF-betaRII) gene. Transfection of the cloned cDNA for human TGF-betaRII to this mutant cell line restored receptor expression as well as the inhibition in growth by TGF-beta1. In both wild-type and mutant cells stably transfected with TGF-betaRII cDNA, TGF-betaRII coimmunoprecipitated with TGF-beta receptor type I in the presence of ligand. These experiments provide direct evidence for the role of TGF-betaRII in the inhibitory effect of TGF-beta on growth and suggest that TGF-betaRII acts by means of a heteromeric surface complex with TGF-beta receptor type I.