Taiwan cobra phospholipase A 2 elicits posttranscriptional up‐regulation of ADAM17 in human neuroblastoma SK‐N‐SH cells

Taiwan cobra phospholipase A 2 (PLA 2 ) 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 PLA 2 ability to induce ADAM17 maturation, and lysophosphatidylcholine treatment mimicked the effect of PLA 2 . ADAM17 activity measurement, ADAM17 cell surface levels, TNFR2 ectodomain shedding, and ADAM17 mRNA transcription supported that posttranscriptional up‐regulation of ADAM17 occurred in PLA 2 ‐treated SK‐N‐SH cells. PLA 2 treatment induced p38 MAPK activation and ERK inactivation. p38 MAPK activation suppression by SB202190 (p38 MAPK inhibitor) abolished posttranscriptional up‐regulation of ADAM17 in PLA 2 ‐treated cells, while treatment with U0126 (MEK1 and MEK2 inhibitor) increased ADAM17 maturation in SK‐N‐SH cells. Constitutively active MEK1 expression abrogated PLA 2 ‐induced ADAM17 maturation. Taken together, our data indicate that PLA 2 ‐evoked p38 MAPK activation and ERK inactivation are involved in ADAM17 posttranscriptional up‐regulation, and suggest that the action of PLA 2 is catalytic activity‐dependent. J. Cell. Biochem. 111: 148–157, 2010. © 2010 Wiley‐Liss, Inc.