Budworth J, Gescher A
Medical Research Council Toxicology Unit, University of Leicester, UK.
FEBS Lett. 1995 Apr 3;362(2):139-42. doi: 10.1016/0014-5793(95)00227-z.
The hypothesis was tested that 9 kinase inhibitors with diverse specificities for protein kinase C (PKC), including staurosporine and four of its analogues, interfere differently with PKC derived from either the cytosolic or particulate fractions of MCF-7 breast carcinoma cells. GF 109203X inhibited the enzyme identically in either preparation. CGP 41251 and calphostin C inhibited cytosolic PKC more effectively than membrane-derived PKC with ratios of IC50 (cytosolic PKC) over IC50 (membrane-derived PKC) of 0.07 and 0.04, respectively. The other six agents inhibited membrane-derived PKC more potently than cytosolic enzyme. Staurosporine and RO 31 8220 exhibited IC50 ratios of 12.3 and 21.6, respectively. The results suggest that there are dramatic differences between kinase inhibitors in their divergent effects on cytosolic and membrane-derived PKC which should be borne in mind in the interpretation of their pharmacological properties.
本研究检验了一种假设，即9种对蛋白激酶C（PKC）具有不同特异性的激酶抑制剂，包括星形孢菌素及其4种类似物，对源自MCF-7乳腺癌细胞胞质或颗粒部分的PKC的干扰作用不同。GF 109203X在两种制剂中对该酶的抑制作用相同。CGP 41251和钙泊三醇C对胞质PKC的抑制作用比对膜来源PKC更有效，IC50（胞质PKC）与IC50（膜来源PKC）的比值分别为0.07和0.04。其他6种药物对膜来源PKC的抑制作用比对胞质酶更强。星形孢菌素和RO 31 8220的IC50比值分别为12.3和21.6。结果表明，激酶抑制剂对胞质和膜来源PKC的不同作用存在显著差异，在解释其药理特性时应予以考虑。
