EPIDERMAL GROWTH-FACTOR AND TRANSFORMING GROWTH FACTOR-ALPHA - DIFFERENTIAL INTRACELLULAR ROUTING AND PROCESSING OF LIGAND-RECEPTOR COMPLEXES
EPIDERMAL GROWTH-FACTOR AND TRANSFORMING GROWTH FACTOR-ALPHA - DIFFERENTIAL INTRACELLULAR ROUTING AND PROCESSING OF LIGAND-RECEPTOR COMPLEXES
复制标题
DOI：
10.1091/mbc.2.8.599
复制
发表时间：
1991-08-01
期刊：
影响因子：
--
通讯作者：
DERYNCK, R
中科院分区：
文献类型：
--
作者：
EBNER, R;DERYNCK, R
两种结构相关但不同的多肽生长因子，表皮生长因子（EGF）和转化生长因子-α（TGF-α），在与共同的细胞表面EGF/TGF-α-受体相互作用后发挥其活性。两种配体的作用的比较研究已经确定TGF-α在各种生物系统中比EGF更有效。这一观察结果不能用配体对受体的亲和力差异来解释，因为两种因子的亲和力常数非常相似。我们比较了在两种不同的细胞系统中使用EGF或TGF-α的配体-受体复合物的细胞内加工。我们发现TGF-α在比EGF高得多的pH下与EGF/TGF-α受体解离，这可能反映了计算的等电点的实质性差异。在内化后，细胞内TGF-α比EGF更快地被清除，并且与大部分降解的EGF相比，释放的TGF-α的大部分代表未降解的TGF-α。此外，TGF-α不诱导细胞表面受体的完全下调，如用EGF观察到的，这至少部分地导致在TGF-α的情况下，下调后配体结合能力的更快恢复。配体-受体复合物加工的这些差异可以解释为什么TGF-α比EGF发挥更高的活性。
Two structurally related but different polypeptide growth factors, epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha), exert their activities after interaction with a common cell-surface EGF/TGF-alpha-receptor. Comparative studies of the effects of both ligands have established that TGF-alpha is more potent than EGF in a variety of biological systems. This observation is not explained by differences in affinities of the ligands for the receptor, because the affinity-constants of both factors are very similar. We have compared the intracellular processing of ligand-receptor complexes using either EGF or TGF-alpha in two different cell systems. We found that TGF-alpha dissociates from the EGF/TGF-alpha-receptor at much higher pH than EGF, which may reflect the substantial difference in the calculated isoelectric points. After internalization, the intracellular TGF-alpha is more rapidly cleared than EGF, and a substantial portion of the released TGF-alpha represents undegraded TGF-alpha in contrast to the mostly degraded EGF. In addition, TGF-alpha did not induce a complete down-regulation of cell surface receptors, as observed with EGF, which is at least in part responsible for a much sooner recovery of the ligand-binding ability after down-regulation, in the case of TGF-alpha. These differences in processing of the ligand-receptor complexes may explain why TGF-alpha exerts quantitatively higher activities than EGF.