Insulin receptor internalization defect in an insulin-resistant mouse melanoma cell line.
Insulin receptor internalization defect in an insulin-resistant mouse melanoma cell line.
复制标题
胰岛素抵抗小鼠黑色素瘤细胞系中胰岛素受体内化缺陷。
DOI：
10.1021/bi00451a031
复制
发表时间：
1989
期刊：
影响因子：
2.9
通讯作者：
Straus,DS
中科院分区：
文献类型：
--
作者：
Androlewicz,MJ;Brandenburg,DF;Straus,DS
Revised Manuscript Received July 27, 1989 abstract: Previous studies from this laboratory demonstrated that thePG19 mouse melanoma cell line does not exhibit a biological response toinsulin, whereas melanoma x mouse embryo fibroblast hybrids do respond to insulin. To investigate the molecular basis of the insulin resistance of the PG19 melanoma cells, insulin receptors from the insulin-resistant melanoma cells and insulin-sensitive fibroblast x melanoma hybrid cells were analyzed by the technique of photoaffinity labeling using the photoprobe 125I-NAPA-DP-insulin. Photolabeled insulin receptors from the two cell types have identical molecular weights as determined by SDS gel electrophoresis under reducing and nonreducing conditions, indicating that the receptors on the two cell lines are structurally similar. Insulin receptor internalization studies revealed that the hybrid cells internalize receptorsto a high degree at 37 C, whereas the melanoma cells internalize receptors to a very low degree or not at all. The correlation between ability to internalize insulin receptorsand sensitivity to insulin action in this system suggests that uptake of the insulin-receptor complex may be required for insulin action inthese cells. Insulin receptors from the two cell lines autophosphorylate in a similar insulin-dependent manner both in vitro and in intact cells, indicating that insulin receptors on the melanoma and hybrid cells have functional tyrosine protein kinase activity. Therefore, the block in insulin action in the PG19 melanoma cells appears to reside at a step beyond insulin-stimulated receptor autophosphorylation.
