Distribution and modulation of the cellular receptor for transforming growth factor-beta.
Distribution and modulation of the cellular receptor for transforming growth factor-beta.
复制标题
细胞受体的分布和调节，以转化生长因子-beta。
DOI：
10.1083/jcb.105.2.965
复制
发表时间：
1987-08
影响因子：
7.8
通讯作者：
Sporn, M B
中科院分区：
文献类型：
--
作者：
Wakefield, L M;Smith, D M;Masui, T;Harris, C C;Sporn, M B
Scatchard对转化生长因子-β与多种不同细胞类型结合的分析表明，在每种细胞类型上都普遍存在高亲和力(Kd=1-60 PM)的转化生长因子-β受体，这表明转化生长因子-β作用的潜在靶向范围很广。受体亲和力与每个细胞表达的受体数量之间存在强烈的负相关关系(r=+0.85)，因此在较低的转化生长因子-β浓度下，基本上所有细胞都结合了相同数量的转化生长因子-β分子。许多影响细胞对转化生长因子-β的反应的药物并不改变转化生长因子-β与各种细胞类型的结合，提示调节转化生长因子-β与其受体的结合可能不是转化生长因子-β作用的主要控制机制。类似地，体外转化只导致转化生长因子-β的细胞结合的相对较小的变化，并且对于那些表现出配体诱导的受体下调的细胞类型，下调并不广泛。因此，在各种条件下，在给定的细胞类型中也可以观察到细胞类型之间的结合的强烈保守性，并且受体的表达似乎基本上是结构性的。最后，生物非活性形式的转化生长因子-β，占所有12种不同类型细胞分泌的自分泌转化生长因子-β的98%以上，在体外被证明在没有事先激活的情况下不能与受体结合。有人认为，这可能阻止高尔基体中自分泌配体和受体的过早相互作用。
Scatchard analyses of the binding of transforming growth factor-beta (TGF-beta) to a wide variety of different cell types in culture revealed the universal presence of high affinity (Kd = 1-60 pM) receptors for TGF-beta on every cell type assayed, indicating a wide potential target range for TGF-beta action. There was a strong (r = +0.85) inverse relationship between the receptor affinity and the number of receptors expressed per cell, such that at low TGF-beta concentrations, essentially all cells bound a similar number of TGF- beta molecules per cell. The binding of TGF-beta to various cell types was not altered by many agents that affect the cellular response to TGF- beta, suggesting that modulation of TGF-beta binding to its receptor may not be a primary control mechanism in TGF-beta action. Similarly, in vitro transformation resulted in only relatively small changes in the cellular binding of TGF-beta, and for those cell types that exhibited ligand-induced down-regulation of the receptor, down- regulation was not extensive. Thus the strong conservation of binding observed between cell types is also seen within a given cell type under a variety of conditions, and receptor expression appears to be essentially constitutive. Finally, the biologically inactive form of TGF-beta, which constitutes greater than 98% of autocrine TGF-beta secreted by all of the twelve different cell types assayed, was shown to be unable to bind to the receptor without prior activation in vitro. It is proposed that this may prevent premature interaction of autocrine ligand and receptor in the Golgi apparatus.