The activation of GTP-binding proteins (G-proteins) by sodium fluoride+aluminum (A1F4 −) was shown in several cell free systems. In the intact cell, NaF ± aluminum was shown to activate various signal transduction pathways and indirect evidence is in line with effector mechanisms involving regulation of G-protein activity. We have explored the effect of NaF on several components of signal transduction pathways in macrophages. NaF was shown to reduce intracellular ATP levels and to suppress agonist-induced protein tyrosine phosphorylation and reactive oxygen species formation. NaF led to in situ activation of mitogen activated protein kinase, phospholipase A2and Ptdlns-phospholipase C. Addition of A1C13or deferoxamine, a chelator of aluminum, had little or no effect on NaF mediated enzyme activation. The results suggest that at least some of the pleiotropic effects of NaF in intact cells may not be mediated by G-protein activation but rather by depletion of ATP which is essential for protein phosphorylation reactions.
|Number of pages||16|
|Journal||Journal of Basic and Clinical Physiology and Pharmacology|
|State||Published - 1 Jan 1995|