Interference of Ha‐ras with inositol trisphosphate‐mediated Ca2+‐release

FEBS Letters

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