Aluminum fluoride induces phosphatidylinositol turnover, elevation of cytoplasmic free calcium, and phosphorylation of the T cell antigen receptor in murine T cells
O'Shea, J.J.; Urdahl, K.B.; Luong, H.T.; Chused, T.M.; Samelson, L.E.; Klausner, R.D.
Journal of Immunology 139(10): 3463-3469
1987
ISSN/ISBN: 0022-1767 PMID: 2824607 Document Number: 290229
Antigen activation of murine T lymphocytes leads to phosphorylation of three subunits of the murine T cell antigen receptor (L. E. Samelson, M. D. Patel, A. M. Weissman, J.B. Harford, and R. D. Klausner. 1986. Cell 46:1083). Two kinases are activated in this process: protein kinase C which leads to phosphorylation of the .gamma. and, to a lesser extent, the .epsilon. subunits on serine residues and a tyrosine kinase which phosphorylates the p21 subunit (M. D. Patel, L. E. Samelson, and R. D. Klausner. 1987. J. Biol Chem. 262:5831). We sought to determine whether treatment of these cells with NaF could simulate any of these antigen-induced events. Indeed NaF treatment resulted in breakdown of polyphosphoinositides and production of phosphoinositols. This treatment also resulted in a rise in cytosolic free Ca2+. EGTA failed to block this rise suggesting that NaF liberated intracellular stores of Ca2+. Finally NaF treatment resulted in phosphorylation of the .gamma. and .epsilon. chains of the T cell receptor indistinguishable from the effects of phorbol esters. The NaF effect was potentiated by addition of AlCl3 consistent with the view that the active moiety is AlF4-. The AlF4--induced phosphorylations were abolished in cells in which protein kinase C was depleted by prior treatment with phorbol myristate acetate. All of these observations are compatible with the interpretation that the AIF4- phosphorylation is mediated by protein kinase C. Antigen and anti-receptor antibody-induced receptor serine phosphorylation and phosphatidylinositol turnover are blocked by raising intracellular levels of cyclic adenosine monophosphate. In contrast, AlF4--induced effects were insensitive to cyclic adenosine monophosphate.