Hatzfeld J, Miskin R, Reich E
J Cell Biol. 1982 Jan;92(1):176-82. doi: 10.1083/jcb.92.1.176.
Previous studies (Miskin, R., T. G. Easton, and E. Reich, 1970, Cell. 15:1301-1312) have shown that sarcoma virus transformation and tumor promoters reduced the cell surface concentration of acetylcholine receptors (AChR) in differentiating chick embryo myogenic cultures. Both of these agents also induced high rates of plasminogen activator (PA) synthesis in myogenic cultures (Miskin, R., T. G. Easton, A. Maelicke, and E. Reich, 1978, Cell. 15:1287-1300), and the present work was performed to establish whether proteolysis might significantly affect receptor metabolism. Proteolysis in myogenic cultures was modulated by one or more of the following: stimulation of PA synthesis, direct addition of plasmin, removal of plasminogen, or addition of plasmin inhibitors. The results were: (a) When the rates of proteolysis were raised either by addition of plasmin or by stimulating PA synthesis in the presence of plasminogen, both the steady-state concentration and the half-life of surface AChR decreased, but the rate of receptor synthesis was unaffected. (b) The magnitude of these effects, and their dependence on added plasminogen, indicated that proteolysis initiated by plasminogen activation could account almost entirely for the reduction in receptor half-life produced by sarcoma virus transformation and phorbol ester. (c) The rate of receptor synthesis, which is also reduced by viral transformation and tumor promoters, was not modified by proteolysis; hence plasmin action may be responsible for a large part, but not all of the change in surface receptor under these conditions. (d) The plasmin catalysed changes in receptor parameters appear to occur in response to modified membrane metabolism resulting from proteolysis of surface components other than AChR itself.
先前的研究（米斯金，R.，T.G.伊斯顿，和E.赖希，1970年，《细胞》杂志。第15卷：1301 - 1312页）表明，肉瘤病毒转化和肿瘤启动子降低了分化中的鸡胚成肌培养物中乙酰胆碱受体（AChR）的细胞表面浓度。这两种因子还在成肌培养物中诱导了高比率的纤溶酶原激活物（PA）合成（米斯金，R.，T.G.伊斯顿，A.梅利克，和E.赖希，1978年，《细胞》杂志。第15卷：1287 - 1300页），而本研究旨在确定蛋白水解是否可能显著影响受体代谢。成肌培养物中的蛋白水解通过以下一种或多种方式进行调节：刺激PA合成、直接添加纤溶酶、去除纤溶酶原或添加纤溶酶抑制剂。结果如下：（a）当通过添加纤溶酶或在纤溶酶原存在下刺激PA合成来提高蛋白水解速率时，表面AChR的稳态浓度和半衰期均降低，但受体合成速率不受影响。（b）这些效应的大小及其对添加的纤溶酶原的依赖性表明，由纤溶酶原激活引发的蛋白水解几乎可以完全解释肉瘤病毒转化和佛波酯导致的受体半衰期缩短。（c）受体合成速率也会因病毒转化和肿瘤启动子而降低，但不受蛋白水解的影响；因此，在这些条件下，纤溶酶的作用可能是表面受体变化的一大部分，但不是全部原因。（d）纤溶酶催化的受体参数变化似乎是由于除AChR本身之外的表面成分的蛋白水解导致膜代谢改变而发生的。
