Termination of IL-6-induced STAT activation is independent of receptor internalization but requires de novo protein synthesis

The interleukin-6 (IL-6) receptor complex comprises the IL-6 receptor (IL-B R, gp80) and the signal transducer gp130. Binding of IL-6 to its receptor r esults in dimerization of gp130, activation of the Jak/STAT pathway, and in a down-regulation of IL-6 binding sites by endocytosis. The STAT activatio n after stimulation is transient, being maximal after 15-30 min and disappe aring after 60-90 min. The mechanism which leads to the termination of the signal is still unknown. In this paper we have studied whether the down-modulation of the STAT signa l requires the endocytosis of the receptor complex. Our results suggest tha t the desensitization of the IL-6 signal is not due to internalization of t he receptor complex but requires de novo protein synthesis. (C) 2000 Federa tion of European Biochemical Societies.