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

✍ Scribed by Wen-Hsin Liu; Ku-Chung Chen; Yi-Ling Chiou; Shinne-Ren Lin; Long-Sen Chang

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 435 KB
• Volume: 111
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.22681

✦ Synopsis

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.