PMID: 8948433Jun 15, 1995Paper

Signal-transduction-pathway-specific desensitization of expression of orphan nuclear receptor TIS1

The Biochemical Journal
R W LimH Yu

Abstract

Induction of many primary-response genes by a variety of stimuli occurs in a transient manner. The precise mechanism responsible for these transient kinetics is not completely understood. We report here that the orphan nuclear receptor, TIS1, which is a potent sequence-specific transcription factor, was transiently induced by the adrenergic agonist isoprenaline in the C2C12 skeletal-muscle cell line. Moreover, we showed that the rapid decline in mRNA level after peak induction was due in part to a specific desensitization of the isoprenaline-mediated induction pathway. Desensitization of the induction response presumably occurred at the level of the receptor, as agents that either bypass the adrenergic receptor or activate alternative signalling pathways were able to induce TIS1 expression in the desensitized cells. However, stimulation by agents that directly activate intracellular enzymes also resulted in the signal-transduction-pathway-specific desensitization of TIS1 inducibility. Our results suggest that the pathway-specific nature of the desensitization process may be important for directing an integrated response to multiple physiological stimuli.

Citations

Jun 26, 2002·The Journal of Biological Chemistry·K D Senali Abayratna WansaGeorge E O Muscat
Jul 11, 2006·American Journal of Physiology. Cell Physiology·Aaron G Smith, George E O Muscat
Oct 26, 1999·Endocrine Reviews·V Giguère
Mar 8, 2006·The Journal of Experimental Medicine·Huiyan ZengHarold F Dvorak
Jul 18, 2014·Endocrinology and Metabolism·Kwi-Hyun BaeKeun-Gyu Park
Jun 20, 2003·Proceedings of the National Academy of Sciences of the United States of America·Shinobu SuzukiWen-Chen Yeh
Oct 13, 2005·Physiological Genomics·Timo KanzleiterMartin Klingenspor
Apr 11, 2006·Nuclear Receptor Signaling·Megan A Maxwell, George E O Muscat

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