Differential signalling potential of insulin‐ and IGF‐1‐receptor cytoplasmic domains.
Differential signalling potential of insulin‐ and IGF‐1‐receptor cytoplasmic domains.
复制标题
胰岛素和 IGF-1 受体胞质结构域的差异信号传导潜力。
DOI：
10.1002/j.1460-2075.1989.tb03517.x
复制
发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Axel Ullrich
中科院分区：
文献类型：
--
作者：
R. Lammers;A. Gray;Joseph Schlessinger;Axel Ullrich
胰岛素样生长因子1（IGF-1）和胰岛素的人受体，以及由配体结合、细胞外胰岛素受体和细胞内IGF-1受体结构组成的两种嵌合受体，已在NIH-3T3成纤维细胞中表达。所有四种受体类型都被合成、加工并转运到细胞表面以形成高亲和力结合位点。所有正常和嵌合受体都有一个活性酪氨酸激酶，分别受同源或异源配体的调节。此外，细胞表面受体被有效内化，并在配体存在下加速降解。虽然所有四种类型的受体刺激葡萄糖转运具有相似的效率，他们表现出显着的差异，在其促有丝分裂信号的潜力。具有IGF-1受体胞质结构域的受体在刺激DNA合成方面的活性是胰岛素受体的10倍。在过度表达野生型和嵌合受体的NIH-3T3细胞中，单独使用IGF-1或胰岛素获得的最大生长反应与使用10%胎牛血清获得的反应相当。我们的结论是，在所采用的细胞系统中，IGF-1和胰岛素的受体类似地介导短期反应，但在其长期促有丝分裂信号传导潜力中显示出不同的特征。
The human receptors for insulin‐like growth factor 1 (IGF‐1) and insulin, and two chimeric receptors consisting of ligand‐binding, extracellular insulin receptor and intracellular IGF‐1 receptor structures, have been expressed in NIH‐3T3 fibroblasts. All four receptor types were synthesized, processed and transported to the cell surface to form high‐affinity binding sites. All normal and chimeric receptors had an active tyrosine kinase which was regulated by homologous or heterologous ligands respectively. In addition, cell surface receptors were internalized efficiently and subjected to accelerated degradation in the presence of ligand. While all four types of receptor stimulated glucose transport with similar efficiency, they displayed significant differences in their mitogenic signalling potentials. Receptors with an IGF‐1 receptor cytoplasmic domain were 10 times more active in stimulating DNA synthesis than the insulin receptor. In NIH‐3T3 cells overexpressing wild‐type and chimeric receptors, maximal growth responses obtained with IGF‐1 or insulin alone were equivalent to those obtained with 10% fetal calf serum. We conclude that in the cell system employed the receptors for IGF‐1 and insulin mediate short‐term responses similarly, but display distinct characteristics in their long‐term mitogenic signalling potentials.