1 The regulatory e ects of transforming growth factor (TGF)-a on phospholipase A 2 (PLA 2 ) isozymes contributing to prostaglandin generation in rat gastric epithelial RGM1 cells were examined.2 Stimulation with TGF-a for 24 h time-dependently induced prostaglandin E 2 generation with an increase in cyclo-oxygenase-2 protein. The TGF-a-induced prostaglandin E 2 generation was suppressed by NS-398, a cyclo-oxygenase-2 inhibitor. 3 TGF-a stimulated the activity and the protein synthesis of cytosolic PLA 2 (cPLA 2 ). A timedependent increase in cPLA 2 protein occurred in parallel with PGE 2 generation, which was inhibited by methyl arachidonyl¯uorophosphonate (MAFP), a cPLA 2 inhibitor. However, no change in activity of secretory PLA 2 or Ca +2 -independent PLA 2 was observed in the TGF-a-stimulated cells. 4 Stimulation with the Ca 2+ ionophore A23187 for 10 min induced MAFP-sensitive arachidonic acid liberation. Interestingly, preincubation with TGF-a for 24 h diminished A23187-stimulated arachidonic acid liberation despite the increase in cPLA 2 protein.5 Under the conditions, TGF-a was found to increase p11, an endogenous cPLA 2 suppressor, also known as annexin II light chain. The TGF-a-induced increase in p11 was suppressed by tyrphostin AG1478, an inhibitor of tyrosine kinase of epidermal growth factor receptor, which was also found to restore the inhibition by TGF-a of A23187-stimulated arachidonic acid liberation. However, TGF-a did not alter protein levels of annexin II heavy chain. 6 These results suggest that TGF-a stimulates prostaglandin generation through an increase in cPLA 2 , the hydrolytic action of which may be under the control of p11.

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