Taiwan cobra phospholipase A₂ elicits posttranscriptional up-regulation of ADAM17 in human neuroblastoma SK-N-SH cells

Taiwan cobra phospholipase A₂ (PLA₂) treatment promoted proADAM17 processing into mature ADAM17 in human neuroblastoma SK-N-SH cells. The abolishment of catalytic activity caused a drastic drop in the PLA₂ ability to induce ADAM17 maturation, and lysophosphatidylcholine treatment mimicked the effect of PLA₂. ADAM17 activity measurement, ADAM17 cell surface levels, TNFR2 ectodomain shedding, and ADAM17 mRNA transcription supported that posttranscriptional up-regulation of ADAM17 occurred in PLA₂-treated SK-N-SH cells. PLA₂ treatment induced p38 MAPK activation and ERK inactivation. p38 MAPK activation suppression by SB202190 (p38 MAPK inhibitor) abolished posttranscriptional up-regulation of ADAM17 in PLA₂-treated cells, while treatment with U0126 (MEK1 and MEK2 inhibitor) increased ADAM17 maturation in SK-N-SH cells. Constitutively active MEK1 expression abrogated PLA₂-induced ADAM17 maturation. Taken together, our data indicate that PLA₂-evoked p38 MAPK activation and ERK inactivation are involved in ADAM17 posttranscriptional up-regulation, and suggest that the action of PLA₂ is catalytic activity-dependent.