Analysis of Signal Transduction in Immunocompetent Cells by Protein Phosphatase and its Application for Autoimmune Disease

以小鼠淋巴组织粗提物为酶源，对蛋白磷酸酶PP1、PP2A和PP2C的不同测定条件进行了研究。在此条件下，测定了MRL/LPR小鼠、自身免疫倾向小鼠和对照组的蛋白磷酸酶活性。在MRL/LPR小鼠中，蛋白磷酸酶活性发生了显著的变化。在MRL/LPR小鼠的脾和肝脏中，PP1和PP2A的活性明显高于对照组。MRL/LPR小鼠脾、肝组织中PP2A活性的升高可能是由于MRL/LPR小鼠出现的异常淋巴细胞聚集所致。虽然MRL/LPR淋巴结节的PP1活性低于正常脾和胸腺，但经Co~(2+)和Gt；-胰酶处理后，其PP1活性显著升高，因此MRL/LPR淋巴结节的PP1活性是所有被检测组织中最高的。相比之下，在自身免疫性疾病模型小鼠中，PP2C活性没有明显变化。然后，用从小鼠淋巴组织制备的T、B、Mphi细胞检测蛋白磷酸酶活性，也证实了PP1活性的变化。这些结果证明了这种疾病组织中蛋白去磷酸化的特异性增强，这为解释MRL/LPR小鼠的信号转导缺陷提供了新的可能性。

The differential assay conditions for protein phoshatases PP1, PP2A and PP2C were extensively studied by using crude extracts from mouse lymphoid tissues as enzyme sources. Under these conditions, the protein phosphatase activities were measured in MRL/lpr mice, autoimmune prone mice, and the control. In MRL/lpr mice, significant alterations in protein phosphatase activities were demonstrated. In spleen and liver from MRL/lpr mice, activities of PP1 and PP2A were distinctively elevated than those of the control mice. The increases in PP2A activity of MRL/lpr spleen and liver were taken to be due to accumulation of the abnormal lymphocytes emerged in MRL/lpr mice. Although the PP1 activity in MRL/lpr lymph nodes was nodes lower than those of normal spleen and thymus, it was greatly increased by Co^<2+>-trypsin treatment so that the PP1 activity of MRL/lpr lymph nodes was the highest among those all the tissues examined. In contrast, PP2C activities showed no remarkable alterations in the autoimmune disease model mice. Then, the protein phosphatase activities were measured by using T, B, Mphi cells prepared from mouse lymphoid tissues, and the alterations in PP1 activity was also confirmed. These results demonstrated a specific elevation in potency of protein dephosphorylation in the tissues with this disease, a new possibility to explain the defect in signal transduction in the MRL/lpr mice.