Hamel F G, Siford G L, Jones J, Duckworth W C
Research Service, Department of Veterans Affairs Medical Center-R151, Omaha, NE 68105, USA.
Mol Cell Endocrinol. 1997 Feb 7;126(2):185-92. doi: 10.1016/s0303-7207(96)03981-0.
Transforming growth factor alpha (TGF alpha) and epidermal growth factor (EGF) bind to the same receptor, but have different potencies and actions. A possible mechanism is that differences in processing may be responsible for their divergent properties. We have examined TGF alpha and EGF processing in isolated rat hepatocytes with and without various protease inhibitors and inhibitors of endosomal processing. Our results show that EGF undergoes limited degradation in endosomes and is primarily degraded in lysosomes. In contrast, TGF alpha is rapidly degraded in endosomes by insulin-degrading enzyme (EC 3.4.24.56), possibly allowing rapid return of the receptor to the cell surface. Incubation of isolated endosomes preloaded with labeled TGF alpha reveals that degradation can occur whether the vesicles are acidified or not, as is also the case for insulin. We conclude that TGF alpha is degraded immediately after internalization, at least partly before acidification has occurred, while EGF requires prolonged intracellular residence and lysosomal degradation. The different degradation pathways may play a role in the different activities of the two hormones.
转化生长因子α（TGFα）和表皮生长因子（EGF）与同一受体结合，但具有不同的效力和作用。一种可能的机制是，加工过程中的差异可能导致它们的特性不同。我们研究了在有或没有各种蛋白酶抑制剂和内体加工抑制剂的情况下，分离的大鼠肝细胞中TGFα和EGF的加工情况。我们的结果表明，EGF在内体中经历有限的降解，主要在溶酶体中降解。相比之下，TGFα在内体中被胰岛素降解酶（EC 3.4.24.56）快速降解，这可能使受体迅速回到细胞表面。用标记的TGFα预加载的分离内体的孵育表明，无论囊泡是否酸化，降解都可能发生，胰岛素也是如此。我们得出结论，TGFα在内化后立即降解，至少部分是在酸化发生之前，而EGF需要在细胞内长时间停留并在溶酶体中降解。不同的降解途径可能在这两种激素的不同活性中起作用。
