Secretory phospholipase A(2) induces phospholipase C gamma-1 activation and Ca2+ mobilization in the human astrocytoma cell line 1321N1 by a mechanism independent of its catalytic activity

The effect of secretory phospholipase A(2) (sPLA(2)) on intracellular Ca2signaling in human astrocytoma cells was studied. sPLA(2) increased cytosol ic [Ca2+] ([Ca2+](c)) in both Ca2+-containing and Ca2+-free medium, thus su ggesting Ca2+ release from intracellular stores. The activation by sPLA(2) of arachidonate release via cytosolic PLA(2) (cPLA(2)) was also independent of extracellular Ca2+. As sPLA(2) requires Ca2+ for activity, these result s indicate that both Ca2+ mobilization and cPLA(2) activation induced by sP LA(2) are unrelated to phospholipase activity but dependent on signaling me chanisms. The sPLA(2)-induced [Ca2+](c) peak was sensitive to Bordetella pe rtussis toxin and inhibited by caffeine, suggesting its mediation by inosit ol 1,4,5-trisphosphate (IP3). sPLA(2) induced tyrosine phosphorylation and membrane targeting of phospholipase C gamma-1 (PLC gamma-1). Moreover, the Ca2+ peak was sensitive to protein tyrosine kinase inhibitors. sPLA(2) acti vates two signaling pathways: one leading to the activation of the MAP kina se/cPLA(2) cascade and another leading to PLC gamma activation and Ca2+ rel ease. (C) 1999 Academic Press.