Decker S J
Rockefeller University, New York, NY 10021.
Biochem Biophys Res Commun. 1990 Jan 30;166(2):615-21. doi: 10.1016/0006-291x(90)90853-f.
The capacity of epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha) to induce internalization and degradation of the EGF receptor was compared in NIH-3T3 cells expressing the human EGF receptor. This study was initiated following the observation that TGF-alpha was much less efficient relative to EGF in generating a Mr = 125,000 amino-terminally truncated degradation product from the mature EGF receptor (EGF-dependent generation of this degradation product is described in S.J. Decker, J. Biol. Chem., 264:17641-17644). Pulse-chase experiments revealed that EGF generally stimulated EGF receptor degradation to a greater extent than TGF-alpha. Both ligands induced EGF receptor internalization to similar degrees. However, recovery of [125I]-EGF binding following incubation with EGF or TGF-alpha was much faster for TGF-alpha treated cells. Recovery of [125I]-EGF binding after TGF-alpha treatment did not appear to require protein synthesis. Tyrosine phosphorylation of EGF receptor from cells treated with TGF-alpha decreased more rapidly following removal of TGF-alpha compared to cells treated similarly with EGF. These data suggest that EGF routes the EGF receptor directly to a degradative pathway, whereas TGF-alpha allows receptor recycling prior to degradation, and that tyrosine phosphorylation could play a role in this differential receptor processing.
在表达人表皮生长因子（EGF）受体的NIH-3T3细胞中，比较了表皮生长因子（EGF）或转化生长因子-α（TGF-α）诱导EGF受体内化和降解的能力。本研究始于观察到，相对于EGF，TGF-α在从成熟EGF受体产生分子量为125,000的氨基末端截短降解产物方面效率要低得多（S.J. Decker在《生物化学杂志》264:17641 - 17644中描述了这种降解产物的EGF依赖性产生）。脉冲追踪实验表明，EGF通常比TGF-α更能刺激EGF受体的降解。两种配体诱导EGF受体内化的程度相似。然而，对于用TGF-α处理的细胞，与EGF或TGF-α孵育后[¹²⁵I]-EGF结合的恢复要快得多。TGF-α处理后[¹²⁵I]-EGF结合的恢复似乎不需要蛋白质合成。与用EGF进行类似处理的细胞相比，去除TGF-α后，用TGF-α处理的细胞中EGF受体的酪氨酸磷酸化下降得更快。这些数据表明，EGF将EGF受体直接导向降解途径，而TGF-α允许受体在降解之前进行再循环，并且酪氨酸磷酸化可能在这种不同的受体加工过程中起作用。
