Stefan C, Wera S, Stalmans W, Bollen M
Division of Biochemistry, Faculty of Medicine, Catholic University of Leuven, Belgium.
Diabetes. 1996 Jul;45(7):980-3. doi: 10.2337/diab.45.7.980.
The membrane protein plasma cell differentiation antigen 1 (PC-1) has been purified as an inhibitor of insulin receptor tyrosine kinase activity and has been implicated in the pathogenesis of NIDDM. However, we show here that PC-1 is a general protein kinase inhibitor in vitro and that this inhibition results from the hydrolysis of ATP by the intrinsic nucleotide pyrophosphatase activity of PC-1. Thus, the inhibition diminished with increasing ATP concentrations, and it was nullified when the ATP concentration was kept constant with a regenerating system or when ATP was added repetitively. When care was taken to avoid ATP depletion, PC-1 did not affect the insulin sensitivity of insulin receptor autophosphorylation. We conclude that the reported inhibition of insulin signaling by PC-1 does not result from a direct inhibition of the insulin receptor kinase activity.
膜蛋白浆细胞分化抗原1（PC-1）已被纯化作为胰岛素受体酪氨酸激酶活性的抑制剂，并与非胰岛素依赖型糖尿病（NIDDM）的发病机制有关。然而，我们在此表明，PC-1在体外是一种通用的蛋白激酶抑制剂，这种抑制作用源于PC-1内在的核苷酸焦磷酸酶活性对ATP的水解。因此，随着ATP浓度的增加，抑制作用减弱，当通过再生系统使ATP浓度保持恒定或重复添加ATP时，抑制作用消失。当注意避免ATP耗竭时，PC-1不会影响胰岛素受体自身磷酸化的胰岛素敏感性。我们得出结论，报道的PC-1对胰岛素信号传导的抑制作用并非源于对胰岛素受体激酶活性的直接抑制。
