title: Taiwan cobra phospholipase A2 elicits posttranscriptional up-regulation of ADAM17 in human neuroblastoma SK-N-SH cells.
abstract: 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.
authors.affiliation: Institute of Biomedical Sciences, National Sun Yat-Sen University-Kaohsiung Medical University Joint Research Center, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.
authors.forename: Wen-Hsin
authors.initials: WH
authors.lastname: Liu
authors.forename: Ku-Chung
authors.initials: KC
authors.lastname: Chen
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Chiou
authors.forename: Shinne-Ren
authors.initials: SR
authors.lastname: Lin
authors.forename: Long-Sen
authors.initials: LS
authors.lastname: Chang
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000072198:ADAM17 Protein; D000818:Animals; D045744:Cell Line, Tumor; D004546:Elapid Venoms / Q000201:enzymology* / Q000494:pharmacology*; D017815:Elapidae; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism*; D054467:Phospholipases A2 / Q000494:pharmacology*; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D004546:Elapid Venoms; D034741:RNA, Small Interfering; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D054467:Phospholipases A2; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human