Interferon-alpha-induced phosphorylation and activation of cytosolic phospholipase A(2) is required for the formation of interferon-stimulated gene factor three

Treatment of cells with interferon (IFN)-alpha caused phosphorylation and activation of cytosolic phospholipase A(2) (cPLA(2)). The protein tyrosine kinase Jak1 was found to be necessary for the activation of cPLA(2). Jak1 could be co-immunoprecipitated with cPLA(2) from cell extracts, indicating that a close physical interaction occurs between these two proteins. The induction of IFN-stimulated gene factor three (ISGF3) by IFN-alpha, is blocked by cPLA(2) inhibitors in cell cultures and in cell-free reconstituted systems. However, these inhibitors do not block IFN-alpha- or gamma-induced binding of STAT1 to the inverted repeat (IR) element of the IFN regulatory factor 1 (IRF-1) gene. Thus, cPLA(2) activation occurs as an early event in the IFN-alpha response and is selectively involved in ISGF3-dependent gene activation.