DEFECT OF INSULIN-RECEPTOR IN INSULIN-RESISTANT VARIANTS OF CLOUDMAN-S91 MOUSE MELANOMA-CELLS

被引：4
作者：
SLOMINSKI, A
MCNEELY, T
PAWELEK, J
机构：
[1] Department of Microbiology, Immunology and Molecular Genetics, Albany Medical College, Albany, NY, 12208
[2] Department of Biochemistry, University of Kentucky, Lexington, KY
[3] Department of Dermatology, Yale University School of Medicine, New Haven, CT, 06510
来源：
MELANOMA RESEARCH | 1992年 / 2卷 / 02期
关键词：
GROWTH REGULATION; INSULIN; INSULIN RECEPTOR; RECEPTOR PROTEOLYSIS;
D O I：
10.1097/00008390-199207000-00006
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
To study the mechanisms by which insulin regulates proliferation, we have compared wild-type Cloudman melanoma cells, whose growth in inhibited by insulin (ins(inh)) to variant lines that were genetically selected for resistance to insulin (ins(res)). Scatchard analysis of insulin binding to five ins(res)) lines and six ins(res) variants revealed a marked reduction in the number of high-affinity binding sites for insulin in the ins(res) lines, and ins(res) lines displayed an abnormal beta-subunit of the insulin receptor. During autophosphorylation of the wheat germ agglutinin-purified receptor, the beta-subunit apparently underwent proteolytic degradation. This proteolysis was ATP-dependent and was prevented by bovine pancreatic trypsin inhibitor, and phenylmethylsulphonyl fluoride, but not by aprotinin or leupeptin. Receptor proteolysis was not observed in wild-type lines. The results suggest that insulin resistance in the mutant Cloudman melanoma cells is apparently due to proteolysis of the beta-subunit of insulin receptor which, in turn, alters insulin binding capacity of the cells and blocks their anti-proliferative response to the hormone.
引用
收藏
页码：115 / 122
页数：8
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