Davis R J, Faucher M, Racaniello L K, Carruthers A, Czech M P
Department of Biochemistry, University of Massachusetts Medical School, Worcester 01605.
J Biol Chem. 1987 Sep 25;262(27):13126-34.
The transferrin receptor cycles rapidly between cell surface and endosomal membrane compartments. Treatment of cultured cells with epidermal growth factor (EGF) or insulin-like growth factor I (IGF-I) at 37 degrees C causes a rapid redistribution of transferrin receptors from an intracellular compartment to the cell surface. The effects of EGF and IGF-I on the kinetics of the cycling of the transferrin receptor in A431 human epidermoid carcinoma cells were compared. The primary site of EGF action was found to be an increase in the rate of transferrin receptor exocytosis. The exocytotic rate constant was measured to be 0.11 min-1 in control cells and 0.33 min-1 in EGF-treated cells. In contrast, IGF-I was found to increase the cell surface expression of transferrin receptors by causing a small increase in the rate of exocytosis (from 0.11 to 0.17 min-1) and a decrease in the rate of endocytosis (from 0.33 to 0.24 min-1). It is concluded that the mechanisms for EGF and IGF-I action to increase the cell surface expression of the transferrin receptor are distinct. A kinetic model of the cycling of the transferrin receptor based on experimentally determined rate constants is presented. The model predicts that a consequence of IGF-I action on transferrin receptor cycling is to decrease the apparent Km for the uptake of diferric transferrin by cells. This prediction is confirmed by direct measurement of the accumulation of 59Fe-labeled diferric transferrin by A431 cells. These data demonstrate that the accumulation of iron by cultured cells is a complex function of the rate of cycling of the transferrin receptor and that this process is under acute regulation by growth factors.
转铁蛋白受体在细胞表面和内体膜区室之间快速循环。在37℃用表皮生长因子（EGF）或胰岛素样生长因子I（IGF-I）处理培养的细胞，会导致转铁蛋白受体从细胞内区室快速重新分布到细胞表面。比较了EGF和IGF-I对A431人表皮样癌细胞中转铁蛋白受体循环动力学的影响。发现EGF作用的主要位点是转铁蛋白受体胞吐速率的增加。在对照细胞中测得的胞吐速率常数为0.11分钟-1，在EGF处理的细胞中为0.33分钟-1。相比之下，发现IGF-I通过使胞吐速率略有增加（从0.11到0.17分钟-1）和内吞速率降低（从0.33到0.24分钟-1）来增加转铁蛋白受体的细胞表面表达。得出的结论是，EGF和IGF-I增加转铁蛋白受体细胞表面表达的作用机制是不同的。提出了基于实验确定的速率常数的转铁蛋白受体循环动力学模型。该模型预测，IGF-I对转铁蛋白受体循环作用的一个结果是降低细胞摄取双铁转铁蛋白的表观Km值。通过直接测量A431细胞对59Fe标记的双铁转铁蛋白的积累，证实了这一预测。这些数据表明，培养细胞中铁的积累是转铁蛋白受体循环速率的复杂函数，并且该过程受到生长因子的急性调节。
