FEBS Letters | |
Interference of Ha‐ras with inositol trisphosphate‐mediated Ca2+‐release | |
Maly, Karl1  Oberhuber, Hermann1  Kiani, Alexander1  Grunicke, Hans1  | |
[1] Institute of Medical Chemistry and Biochemistry, A-6020 Innsbruck, Austria | |
关键词: NIH3T3 fibroblast; Harvey-ras; Calcium; Inositolphosphate; Bombesin; DMEM; Dulbecco's modified Eagle's medium; Dex; dexamethasone; EGTA; [ethylene-bis-(oxyethylene-nitrilo)]tetraacetic acid; FCS; fetal calf serum; PBS; Phosphate buffered saline; HBS; HEPES-buffered saline; HEPES; 4-(2-hydroxyethyl)-1-piperazineethane-sulfonic acid; IP3; inositol-1; 4; 5-trisphosphate; MMTV-LTR; mouse mammary tumor virus long terminal repeat; | |
DOI : 10.1016/0014-5793(91)81116-P | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
Expression of a transforming Ha-ras by dexamethasone in NIH3T3 cells transfected with a glucocorticoid-inducible Ha-ras construct results in a rapid desensitization of the intracellular Ca2+-mobilizing system to bombesin. This effect precedes the down-modulation of inositol trisphosphate (IP3) formation by several hours and is, therefore, not explained by an uncoupling of phosphoinositidase C. It is demonstrated that expression of Ha-ras attenuates the Ca2+-release by IP3 in permeabilized cells. The IP3 concentration required for half-maximal Ca2+-release is doubled in Ha-ras expressing cells. Maximal Ca2+-release which is obtained with 2,μM IP3 in control cells requires 10μM IP3 in cells expressing Ha-ras. The desensitization of the IP3 receptors coincides with the desensitization of the Ca2+-mobilizing system to bombesin. The results indicate that the Ha-ras mediated desensitization of the Ca2+-releasing system to bombesin is — at least in part — caused by a decrease in the affinity of the IP3 receptor to inositol trisphosphate.
【 授权许可】
Unknown
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