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：1987
卷号：84
期号：15
页码：5247-5251
DOI：10.1073/pnas.84.15.5247
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：We show that Cloudman melanoma cells undergo rapid arborization in response to [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone, a potent analogue of alpha-melanocyte stimulating hormone (alpha-MSH). The arbors were established by extension of processes and resembled dendrites. We used this system to study the regulation of cell shape. alpha-MSH is known to induce increases in cAMP levels, and agents such as forskolin and isobutylmethylxanthine that led to increased cAMP also caused arborization. However, equally dramatic arbors were formed after incubation with the protein kinase C inhibitor H-7 [1-(5-isoquinolinesulfonyl)-alpha-methyl-piperazine]. Phorbol diesters that activate protein kinase C led to cell rounding and antagonized alpha-MSH. The actions of protein kinase C cannot be rationalized in terms of indirect effects on cAMP: neither H-7 nor phorbol diesters alone altered cAMP levels, nor did they affect the increase in cAMP induced by MSH. We show also that MSH produced longer-term effects that cannot be mimicked by cAMP. Specifically, even in the continued presence of alpha-MSH, arborization was followed by morphological reversal to the unstimulated flattened configuration within 2 hr. (This did not occur with other agents that increase cAMP or with H-7.) Most importantly, whereas MSH-induced arborization occurred in the presence of cycloheximide, actinomycin D, or in enucleated cells, the reversal of arborization did not. Thus, MSH induced a program of rapid shape change that was dependent on new protein synthesis and gene transcription.
