期刊
JOURNAL OF PINEAL RESEARCH
卷 44, 期 3, 页码 288-298出版社
WILEY
DOI: 10.1111/j.1600-079X.2007.00525.x
关键词
differentiation; endocytosis; MEK1/2; melatonin; melatonin receptors; microtubules; beta-arrestin
资金
- NIDDK NIH HHS [R15 DK 54070-01A1] Funding Source: Medline
- NINDS NIH HHS [R15 NS37672] Funding Source: Medline
Melatonin induces cellular differentiation in numerous cell types. Data show that multiple mechanisms are involved in these processes that are cell-type specific and may be receptor dependent or independent. The focus of this study was to specifically assess the role of human MTI melatonin receptors in cellular differentiation using an MT1-Chinese hamster ovary (CHO) model; one that reproducibly produces measurable morphologic changes in response to melatonin. Using multiple approaches, we show that melatonin induces MT1-CHO cells to hyperelongate through a MEK 1/2, and ERK 1/2-dependent mechanism that is dependent upon MT1 receptor Gi protein activation, and clathrin-mediated endocytosis. internalization, Using immunoprecipitation analysis, we show that MTl receptors form complexes with Gi(alpha) 2,3, Gq(alpha), beta-arrestin-2, MEK 1/2, and ERK 1/2 in the presence of melatonin. We also show that MEK and ERK activity that is induced by melatonin is dependent on Gi protein activation, clathrin-mediated endocytosis and is modulated by microtubules. We conclude from these studies that melatonin-induced internalization of human MT1 melatonin receptors in CHO cells is responsible for activating both MEK 1/2 and ERK 1/2 to drive these morphologic changes. These events, as mediated by melatonin, require Gi protein activation and endocytosis mediated through clathrin, to form MT1 receptor complexes with beta-arrestin-2/MEK 1/2 and ERK 1/2. The MT1-CHO model is invaluable to mapping out signaling cascades as mediated through MTI receptors especially because it separates out MEK/ERK 1/2 activation by MTl receptors from that of receptor tyrosine kinases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据