Pang D T, Shafer J A
J Biol Chem. 1985 Apr 25;260(8):5126-30.
The autophosphorylation reaction responsible for conversion of insulin receptor (from human placenta) to an active tyrosyl-protein kinase was shown to be inhibited by Zn2+ and other divalent metal ions. The order of inhibitory potency was found to be Cu2+ greater than Zn2+, Cd2+ greater than Co2+, Ni2+. Autophosphorylation of insulin receptor was almost completely blocked by 10 microM Zn2+. Zn2+, however, did not appear to affect the binding of insulin to its receptor. Histidine, a chelator of Zn2+, protected against the inhibitory effects of Zn2+. The failure of histidine to regenerate the competence of the Zn2+-inhibited receptor to undergo autophosphorylation suggested that the inhibition by Zn2+ was irreversible. In addition to inhibiting autophosphorylation, Zn2+ inhibited the tyrosyl-protein kinase activity of highly purified phosphorylated receptor. Zn2+ was also observed to inhibit phosphotyrosyl-protein phosphatase activity present in preparations of partially purified insulin receptor. These inhibitory effects of Zn2+ should be considered in the design of protocols for the isolation and handling of insulin receptor and possibly other tyrosine kinases. Additionally, the possible physiological significance of the inhibition of insulin receptor kinase by Zn2+ is discussed in light of the fact that Zn2+ is accumulated in and secreted from pancreatic islet cells together with insulin.
负责将胰岛素受体（来自人胎盘）转化为活性酪氨酰蛋白激酶的自磷酸化反应被证明会受到Zn2+和其他二价金属离子的抑制。发现抑制效力的顺序为：Cu2+大于Zn2+，Cd2+大于Co2+，Ni2+。10微摩尔的Zn2+几乎完全阻断了胰岛素受体的自磷酸化。然而，Zn2+似乎并不影响胰岛素与其受体的结合。组氨酸作为Zn2+的螯合剂，可防止Zn2+的抑制作用。组氨酸无法恢复Zn2+抑制的受体进行自磷酸化的能力，这表明Zn2+的抑制作用是不可逆的。除了抑制自磷酸化外，Zn2+还抑制了高度纯化的磷酸化受体的酪氨酰蛋白激酶活性。还观察到Zn2+抑制部分纯化的胰岛素受体制剂中存在的磷酸酪氨酰蛋白磷酸酶活性。在设计胰岛素受体以及可能的其他酪氨酸激酶的分离和处理方案时，应考虑Zn2+的这些抑制作用。此外，鉴于Zn2+与胰岛素一起在胰岛细胞中积累并分泌，讨论了Zn2+抑制胰岛素受体激酶可能的生理意义。
