title: Roles of C-terminal processing, and involvement in transacylation reaction of human group IVC phospholipase A2 (cPLA2gamma).
abstract: The phospholipase A2s (PLA2s) are a diverse group of enzymes that hydrolyze the sn-2 fatty acid from phospholipids and play a role in a wide range of physiological functions. A 61-kDa calcium-independent PLA2, termed cPLA2gamma, was identified as an ortholog of cPLA2alpha with approximately 30% overall sequence identity. cPLA2gamma contains a potential prenylation motif at its C terminus, and is known to have PLA2 and lysophospholipase activities, but its physiological roles have not been clarified. In the present study, we expressed various forms of recombinant cPLA2gamma, including non-prenylated and non-cleaved forms, in order to investigate the effects of C-terminal processing. We examined the expression of the wild type and non-prenylated (SCLA) forms of cPLA2gamma, and found that the SCLA form was expressed normally and retained almost full activity. Expression of the prenylated and non-cleaved form of cPLA2gamma using yeast mutants lacking prenyl protein proteases AFC1 (a-factor-converting enzyme) and RCE1 (Ras-converting enzyme) revealed decreased expression in the mutant strain compared to that in the wild type yeast, suggesting that complete C-terminal processing is important for the functional expression of cPLA2gamma. In addition, cPLA2gamma was found to have coenzyme A (CoA)-independent transacylation and lysophospholipid (LPL) dismutase (LPLase/transacylase) activities, suggesting that it may be involved in fatty acid remodeling of phospholipids and the clearance of toxic lysophospholipids in cells.
authors.affiliation: Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195. ayamashi@pharm.teikyo-u.ac.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamashita
authors.forename: Ryo
authors.initials: R
authors.lastname: Kamata
authors.forename: Norikazu
authors.initials: N
authors.lastname: Kawagishi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sugiura
authors.forename: Keizo
authors.initials: K
authors.lastname: Waku
mesh_terms: D000215:Acylation; D000818:Animals; D002460:Cell Line; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism; D054513:Group IV Phospholipases A2; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D008956:Models, Chemical; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D043484:Proprotein Convertases; D011499:Protein Processing, Post-Translational / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D018411:Spodoptera
chemical_list: D008246:Lysophospholipids; D008565:Membrane Proteins; D010743:Phospholipids; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D010741:Phospholipases A; D054513:Group IV Phospholipases A2; D054467:Phospholipases A2; D010450:Endopeptidases; D043484:Proprotein Convertases; C105193:RCE1 protein, S cerevisiae; D008666:Metalloendopeptidases; C491251:STE24 protein, S cerevisiae