Laiho M, Weis M B, Massagué J
Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
J Biol Chem. 1990 Oct 25;265(30):18518-24.
A panel of 71 chemically mutagenized Mv1Lu mink lung epithelial cell clones were selected based on their resistance to the growth inhibitory action of transforming growth factor beta 1 (TGF-beta 1) and TGF-beta 2. Characterization of TGF-beta receptors in these mutants indicates that the TGF-beta-binding membrane proteoglycan, betaglycan, is apparently normal in all of them. However, 14 of the mutant clones are defective in TGF-beta receptor type I, and 22 clones are simultaneously defective in receptor types I and II. The clones with type I receptor defects fall into two distinct phenotypes, called R and LR. The R phenotype is characterized by the lack of detectable type I receptors, and has been previously described (Boyd, F. T., and Massagué, J. (1989) J. Biol. Chem. 264, 2272-2278). LR mutants are characterized by expression of low levels of type I receptor and are, like the R mutants, completely resistant to growth inhibition by TGF-beta 1 or -beta 2. Mutant clones that are simultaneously defective in receptor types I and II fall into three distinct phenotypes. These included DRa mutants which are characterized by lack of detectable receptor types I and II, DRb mutants which are characterized by low expression of both receptor types and an anomalously fast electrophoretic mobility of the type II receptor protein. All mutants that have a low level of type II receptor are also defective in type I receptor. In addition to the loss of growth inhibitory response, the receptor-defective mutants described here have lost all other responses to TGF-beta 1 and -beta 2 known to occur in parental Mv1Lu cells. The defects present in these mutant clones are not encountered in clones isolated from nonmutagenized parental Mv1Lu cells or in mutagenized cells that had not been exposed to selection with TGF-beta. The results implicate TGF-beta receptor types I and II in the mediation of a common set of cellular responses to TGF-beta. Furthermore, the high relative frequency of isolation of DR mutants raises the possibility that receptor types I and II interact as part of a common signaling TGF-beta receptor complex.
基于对转化生长因子β1（TGF-β1）和TGF-β2生长抑制作用的抗性，从71个化学诱变的Mv1Lu貂肺上皮细胞克隆中选出一组克隆。对这些突变体中TGF-β受体的表征表明，TGF-β结合膜蛋白聚糖betaglycan在所有突变体中显然都是正常的。然而，14个突变体克隆在I型TGF-β受体方面存在缺陷，22个克隆在I型和II型受体方面同时存在缺陷。具有I型受体缺陷的克隆分为两种不同的表型，称为R型和LR型。R型表型的特征是缺乏可检测到的I型受体，此前已有描述（Boyd, F. T., and Massagué, J. (1989) J. Biol. Chem. 264, 2272 - 2278）。LR突变体的特征是I型受体表达水平低，并且与R突变体一样，对TGF-β1或-β2的生长抑制完全抗性。在I型和II型受体方面同时存在缺陷的突变体克隆分为三种不同的表型。其中包括DRa突变体，其特征是缺乏可检测到的I型和II型受体；DRb突变体，其特征是两种受体类型的表达水平低，且II型受体蛋白的电泳迁移异常快。所有II型受体水平低的突变体在I型受体方面也存在缺陷。除了失去生长抑制反应外，这里描述的受体缺陷突变体还失去了亲代Mv1Lu细胞中已知的对TGF-β1和-β2的所有其他反应。在从未诱变的亲代Mv1Lu细胞分离的克隆或未用TGF-β进行选择的诱变细胞中未发现这些突变体克隆中存在的缺陷。结果表明I型和II型TGF-β受体参与介导细胞对TGF-β的一组共同反应。此外，DR突变体的高相对分离频率增加了I型和II型受体作为共同信号TGF-β受体复合物的一部分相互作用的可能性。
