Gray G M, Macara I G
Division of Toxicology, University of Rochester Medical Center, New York 14642.
J Biol Chem. 1988 Aug 5;263(22):10714-9.
Protein kinase C (Ca2+/phospholipid-dependent enzyme) is known to phosphorylate the epidermal growth factor receptor and reduce its affinity for epidermal growth factor. Transformation of 3T3 fibroblasts by the oncogenic tyrosine kinase pp60v-src is accompanied by an elevation of cellular diacylglycerol and partial activation of protein kinase C (Wolfman, A., Wingrove, T. G., Blackshear, P. J., and Macara, I. G. (1987) J. Biol. Chem. 262, 16546-16552). We therefore asked whether pp60v-src can down-modulate the epidermal growth factor receptor. We report that within 15 min of activating temperature-sensitive pp60v-src, binding of 125I-labeled epidermal growth factor to 3T3 cells falls at least 50%. Two distinct processes control the down-modulation by pp60v-src. The first is rapid and transient, while the second requires protein synthesis and persists long after inactivation of pp60v-src. Surprisingly, both mechanisms seem to be protein kinase C-independent. Both operate by decreasing the affinity of the epidermal growth factor receptor for its ligand.
蛋白激酶C（一种钙/磷脂依赖性酶）已知可使表皮生长因子受体磷酸化并降低其对表皮生长因子的亲和力。致癌性酪氨酸激酶pp60v-src使3T3成纤维细胞发生转化时，伴随着细胞二酰基甘油水平的升高和蛋白激酶C的部分激活（沃尔夫曼，A.，温格罗夫，T.G.，布莱克希尔，P.J.，以及马卡拉，I.G.（1987年）《生物化学杂志》262卷，16546 - 16552页）。因此，我们探究pp60v-src是否能够下调表皮生长因子受体。我们报告，在激活温度敏感型pp60v-src后的15分钟内，125I标记的表皮生长因子与3T3细胞的结合下降至少50%。pp60v-src的下调作用受两个不同过程控制。第一个过程迅速且短暂，而第二个过程需要蛋白质合成，并且在pp60v-src失活后仍持续很长时间。令人惊讶的是，这两种机制似乎都不依赖蛋白激酶C。两者都是通过降低表皮生长因子受体对其配体的亲和力来发挥作用的。
