Aluminum fluoride inhibits phospholipase D activation by a GTP‐binding protein‐independent mechanism

FEBS Letters

Fleming, Norman¹  Li, Liang¹ 

[1] Department of Oral Biology, University of Manitoba, 780 Bannatyne Avenue, Winnipeg, Man. R3E 0W2, Canada

关键词: Phospholipase D;    Aluminum fluoride;    GTP-binding protein;    Salivary gland;   

DOI  :  10.1016/S0014-5793(99)01196-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Aluminum fluoride (AlF₄ ⁻) inhibited guanine nucleotide-activated phospholipase D (PLD) in rat submandibular gland cell-free lysates in a concentration-dependent response. This effect was consistent in permeabilized cells with endogenous phospholipid PLD substrates. Inhibition was not caused by either fluoride or aluminum alone and was reversed by aluminum chelation. Inhibition of PLD by aluminum fluoride was not mediated by cAMP, phosphatases 1, 2A or 2B, or phosphatidate phosphohydrolase. AlF₄ ⁻ had a similar inhibitory effect on rArf-stimulated PLD, but did not block the translocation of Arf from cytosol to membranes, indicating a post-GTP-binding-protein site of action. Oleate-sensitive PLD, which is not guanine nucleotide-dependent, was also inhibited by AlF₄ ⁻, supporting a G protein-independent mechanism of action. A submandibular Golgi-enriched membrane preparation had high PLD activity which was also potently inhibited by AlF₄ ⁻, leading to speculation that the known fluoride inhibition of Golgi vesicle transport may be PLD-mediated. It is proposed that aluminum fluoride inhibits different forms of PLD by a mechanism that is independent of GTP-binding proteins and that acts via a membrane-associated target which may be the enzyme itself.

【 授权许可】

Unknown