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标题：Cholera Toxin Mimics Melanocyte Stimulating Hormone in Inducing Differentiation in Melanoma Cells
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作者：Edward O'Keefe ; Pedro Cuatrecasas
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1974
卷号：71
期号：6
页码：2500-2504
DOI：10.1073/pnas.71.6.2500
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Cholera toxin (choleragen) and melanocyte stimulating hormone alter within hours the morphology of melanoma cells in culture, and they slow the growth of serum-stimulated cells. After 7-10 days, cells exposed to choleragen or hormone show increased size and a fibroblastic growth pattern. Tyrosinase (EC 1.14.18.1 ; monophenol monooxygenase) activity increases after 3 days in the presence of 10-8 M hormone or 10-10 M choleragen. Binding studies with 125I-labeled choleragen indicate that although a melanoma cell can bind a maximum of 106 molecules of cholera toxin, only about 4000 binding sites must be occupied to achieve maximum stimulation of tyrosinase activity. Melanocyte stimulating hormone and choleragen probably have different membrane-binding sites. After exposure to choleragen for 5 min, membrane adenylate cyclase (EC 4.6.1.1 ) activity increases dramatically upon further incubation of intact cells for several hours at 37{degrees} and falls slowly to basal values over a period of more than 10 days. Hormone stimulation of adenylate cyclase is rapidly reversed by washing the cells, but subsequent restimulation of cyclase by the hormone is impaired. These studies indicate that cAMP mediates the effects of melanocyte stimulating hormone on growth and morphology as well as on tyrosinase activity. Cholera toxin may permanently activate the available adenylate cyclase molecules, and the protracted decay of stimulation that follows may reflect the biological turnover of adenylate cyclase molecules in these cells.
关键词：adenylate cyclase ; membrane receptors ; tyrosinase ; morphology ; cell cycle