Black F M, Wakelam M J
Department of Biochemistry, University of Glasgow, Scotland, U.K.
Biochem J. 1990 May 1;267(3):809-13. doi: 10.1042/bj2670809.
The stimulation of inositol phosphate generation in control and ras-gene-transformed NIH-3T3 cells by prostaglandin F2 alpha (PGF2 alpha) was investigated. Compared with the control cells, a desensitization of the response was observed in cells transformed by the overexpression of N-, Ha-, or Ki-ras genes. This desensitization was without effect upon the concentration causing half-maximal effect (EC50), dissociation constant (Kd) or number of PGF2 alpha receptors. Inhibition of PG synthesis was without effect upon desensitization, demonstrating that the effect was not agonist-induced. Desensitization could be induced in NIH-3T3 cells by culturing under conditions where the cells were all in the exponential growth phase, or by a 12 h exposure to a C-kinase-activating phorbol ester. These results suggest that desensitization of certain agonist-induced inositol phospholipid responses in ras-transformed cells is a consequence of increased cell proliferation and associated amplification in C-kinase activity and is an indirect consequence of transformation by ras.
研究了前列腺素F2α（PGF2α）对对照及ras基因转化的NIH-3T3细胞中肌醇磷酸生成的刺激作用。与对照细胞相比，在通过N-、Ha-或Ki-ras基因过表达而转化的细胞中观察到反应脱敏。这种脱敏对引起半数最大效应的浓度（EC50）、解离常数（Kd）或PGF2α受体数量没有影响。抑制PG合成对脱敏没有影响，表明该效应不是激动剂诱导的。通过在细胞均处于指数生长期的条件下培养，或通过12小时暴露于激活C激酶的佛波酯，可在NIH-3T3细胞中诱导脱敏。这些结果表明，ras转化细胞中某些激动剂诱导的肌醇磷脂反应脱敏是细胞增殖增加以及C激酶活性相关放大的结果，并且是ras转化的间接后果。
