Annexin‐I inhibits PMA‐induced c‐fos SRE activation by suppressing cytosolic phospholipase A2 signal

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Abstract
Annexin‐I (ANX‐I) is a 37‐kDa protein with a calcium‐dependent phospholipid‐binding property. Previously we have observed the inhibition of cytosolic phospholipase A2 (cPLA2) by ANX‐I in the studies using purified recombinant ANX‐I, and proposed a specific interaction model for the mechanism of cPLA2 inhibition by ANX‐I [Kim et al. (1994) FEBS Lett. 343, 251–255]. Here we have studied the role of ANX‐I in the cPLA2 signaling pathway by transient transfection assay. The stimulation of Rat2 fibroblast cells with phorbol 12‐myristate 13‐acetate (PMA) induced the c‐fos serum response element (SRE). The SRE stimulation by PMA was dramatically reduced by (1) pretreatment with a cPLA2‐specific inhibitor, arachidonyltrifluoromethyl ketone, or (2) co‐transfection with antisense cPLA2 oligonucleotide, indicating that the SRE activation was through cPLA2 activation. Co‐transfection with an ANX‐I expression vector also reduced the SRE stimulation by PMA, suggesting the inhibition of cPLA2 by ANX‐I. The active domain of ANX‐I was mapped using various deletion mutants. ANX‐I(1–113) and ANX‐I(34–346) were fully active, whereas ANX‐I(114–346) abolished the activity. Therefore the activity was in the amino acid 34 to 113 region, which corresponds to the conserved domain I of ANX‐I.