Uehara Y
Dept. of Bioactive Molecules, National Institute of Health.
Gan To Kagaku Ryoho. 1997 Jan;24(2):136-44.
Protein kinases are critical enzymes in regulating cellular growth and differentiation. Protein tyrosine kinases are potential targets for new anti-cancer therapeutics because they are encoded by many oncogenes. We first identified herbimycin A as an inhibitor of Src tyrosine kinase by screening agents that cause morphological reversion of v-src oncogene transformed cells. We next developed a method for evaluating inhibitors of oncogenic signal transduction pathways based on different growth abilities between normal and transformed cells in a defined serum free medium and isolated new tyrosine kinase inhibitors angelmicins. Recently, we developed an assay system in which activities of protein kinase A, protein kinase C, protein tyrosine kinase and calmodulin-dependent protein kinase III were simultaneously detected on a single gel. This system should be useful for evaluating specificities and screening of protein kinase inhibitors.
蛋白激酶是调节细胞生长和分化的关键酶。蛋白酪氨酸激酶是新型抗癌疗法的潜在靶点，因为它们由许多癌基因编码。我们首先通过筛选能使v-src癌基因转化细胞发生形态逆转的试剂，鉴定出赫比霉素A是Src酪氨酸激酶的抑制剂。接下来，我们基于正常细胞和转化细胞在特定无血清培养基中的不同生长能力，开发了一种评估致癌信号转导通路抑制剂的方法，并分离出了新的酪氨酸激酶抑制剂安吉尔霉素。最近，我们开发了一种检测系统，可在单一凝胶上同时检测蛋白激酶A、蛋白激酶C、蛋白酪氨酸激酶和钙调蛋白依赖性蛋白激酶III的活性。该系统对于评估蛋白激酶抑制剂的特异性和筛选应是有用的。
