Human Group IVC Phospholipase A2(cPLA2γ)

Asai, Kenji; Hirabayashi, Tetsuya; Houjou, Toshiaki; Uozumi, Naonori; Taguchi, Ryo; Shimizu, Takao

doi:10.1074/jbc.m212117200

Cited by 85 publications

(40 citation statements)

References 55 publications

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“…While little is known of the PLA 1 s potentially involved in remodeling of phospholipids, several types of PLA 2 s, particularly members of the iPLA 2 and cPLA 2 families, have been implicated in this process (49,51,52), albeit most studies have concentrated on PC. The involvement of both iPLAs and cPLAs in aminophospholipid remodeling is supported by the present data obtained with the PLA 2 inhibitors MAFP, R-BEL, and S-BEL.…”

Section: Discussionmentioning

confidence: 99%

“…Phospholipases and acyl transferases/transacylases putatively involved in phospholipid remodeling have been localized to the endoplasmic reticulum, the Golgi, mitochondria, nucleus, and peroxisomes (9,10,18,51,52,(62)(63)(64)(65). It is an intriguing possibility that organelles harbor different sets of remodeling enzymes, which could contribute to their specific phospholipid molecular species profiles.…”

Section: Discussionmentioning

confidence: 99%

“…Particularly the Group VIA Ca 2ϩ -independent phospholipase iPLA 2 ␤ has been frequently implicated (49), albeit contradictory data have been obtained with some cell types (50). Also certain Group IV cytosolic phospholipases (cPLAs) may participate in phospholipid remodeling (51,52).…”

Section: Cyclodextrin-mediated Introduction Of Aminophospholipidmentioning

confidence: 99%

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Electrospray Ionization Mass Spectrometry and Exogenous Heavy Isotope-labeled Lipid Species Provide Detailed Information on Aminophospholipid Acyl Chain Remodeling

Kainu

Hermansson

Somerharju

2008

Journal of Biological Chemistry

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Mammalian cells maintain the phospholipid compositions of their different membranes remarkably constant. Beside de novo synthesis, degradation, and intracellular trafficking, acyl chain remodeling plays an important role in phospholipid homeostasis. However, many key details of this process remain unresolved, largely because of limitations of existing methodologies. Here we describe a novel approach that allows one to study metabolism of individual phospholipid species in unprecedented detail. Forty different phosphatidylethanolamine (PE) or -serine (PS) species with a deuterium-labeled head group were synthesized and introduced to BHK21 or HeLa cells using cyclodextrin-mediated transfer. Their metabolism was then monitored in detail by electrospray ionization mass spectrometry. Atypical PE and PS species were rapidly remodeled at both sn1 and sn2 position, yielding a molecular species profile similar to that the endogenous PE and PS. In contrast, remodeling of exogenous species identical or similar to major endogenous ones was more limited and much slower. Major differences in remodeling pathways and kinetics were observed between species within a class, as well as between corresponding PE and PS species. These data along with those obtained with pharmacological inhibitors strongly suggest that multiple lipid class-specific A-type phospholipases and acyl transferases are involved in aminophospholipid remodeling. In conclusion, the approach described here provides highly detailed information on remodeling of exogenously added (amino)glycerophospholipids and should thus be very helpful when elucidating the proteins and processes maintaining molecular species homeostasis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Electrospray Ionization Mass Spectrometry and Exogenous Heavy Isotope-labeled Lipid Species Provide Detailed Information on Aminophospholipid Acyl Chain Remodeling

Kainu

Hermansson

Somerharju

2008

Journal of Biological Chemistry

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“…17,96,97) cPLA 2 g is activated in response to serum, interleukin-1b, and hydrogen peroxide when it is overexpressed in cells. [96][97][98] The potential upstream signals for cPLA 2 g activation are unknown. cPLA 2 g is constitutively membrane-associated in the ER and Golgi apparatus.…”

Section: Novel Paralogsmentioning

confidence: 99%

Regulatory Mechanism and Physiological Role of Cytosolic Phospholipase A2

Hirabayashi

Murayama

Shimizu

2004

Biological & Pharmaceutical Bulletin

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214

184

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Cytosolic phospholipase A 2 a a (cPLA 2 a a) preferentially hydrolyzes phospholipids containing arachidonic acid and plays a key role in the biosynthesis of eicosanoids. This review discusses the essential features of cPLA 2 a a regulation and addresses new insights into the functional properties of this enzyme. Full activation of the enzyme requires Ca 2؉ binding to an N-terminal C2 domain and phosphorylation on serine residues. Ca 2؉ binding induces translocation of cPLA 2 a a from the cytosol to the perinuclear membranes. Serine phosphorylation is mediated by mitogen-activated protein kinases (MAPKs), Ca 2؉ /calmodulin-dependent protein kinase II, and MAPK-interacting kinase Mnk1. Interaction with proteins and lipids, which include vimentin, annexins, NADPH oxidase, phosphatidylcholine, phosphatidylinositol 4,5-bisphosphate (PIP 2 ), and ceramide-1-phosphate, can also modulate the activity of cPLA 2 a a. Recent evidence has established the physiological and pathological roles of cPLA 2 a a using cPLA 2 a a knockout mice. This enzyme has been implicated in fertility, striated muscle growth, renal concentration, postischemic brain injury, arthritis, inflammatory bone resorption, intestinal polyposis, pulmonary fibrosis, acute respiratory distress syndrome, and autoimmune encephalomyelitis. Now novel three paralogs, cPLA 2 b b, cPLA 2 g g, and cPLA 2 d d, have been identified in humans. cPLA 2 g g is distinct from others in that it is farnesylated and lacks the C2 domain. Biological roles for these new enzymes have not yet been defined.

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“…cPLA 2 ␥, lacking the C2 domain, has Ca 2ϩ -independent PLA 2 activity. A possible function for cPLA 2 ␥ is remodeling of membrane phospholipids (33,34). Recently, human cPLA 2 ␦ was identified as one of psoriasisrelated genes (35).…”

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confidence: 99%

Identification of Novel Cytosolic Phospholipase A2s, Murine cPLA2δ, ϵ, and ζ, Which Form a Gene Cluster with cPLA2β

Ohto

Uozumi

Hirabayashi

et al. 2005

Journal of Biological Chemistry

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127

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Phospholipase A 2 hydrolyzes the sn-2 ester bond of glycerophospholipids that produce free fatty acids and lysophospholipids. Cytosolic phospholipase A 2 s (cPLA 2 , group IV) are a subgroup of enzymes that act on the intracellular phospholipid membrane. The best investigated cPLA 2 ␣ (group IVA) is a key enzyme for lipid mediator production in vivo. Here we report cloning and characterization of novel murine cPLA 2 s: cPLA 2 ␦ (group IVD), cPLA 2 ⑀ (group IVE), and cPLA 2 (group IVF), that form a gene cluster with cPLA 2 ␤ (group IVB). The deduced amino acid sequences of cPLA 2 ␦, ⑀, and demonstrated a conserved domain structure of cPLA 2 , i.e. one C2 domain and one lipase domain. The potential catalytic dyad, Ser and Asp, was conserved for these newly cloned cPLA 2 s along with relatively high conservation for the surrounding residues. Transcripts of murine cPLA 2 ␦, ⑀, and appeared to be enriched in certain organs rather than ubiquitous distribution. Major Northern signals for cPLA 2 ␦ were detected in placenta, cPLA 2 ⑀ in thyroid, heart, and skeletal muscle, and cPLA 2 in thyroid. Recombinant proteins expressed in human embryonic kidney 293 cells demonstrated molecular sizes of about 100 kDa by Western blotting and exhibited Ca 2؉ -dependent PLA 2 activities on 1-palmitoyl-2-[ 14 C]arachidonoyl-phosphatidylcholine substrate. In contrast to cPLA 2 ␣, cPLA 2 preferred phosphatidylethanolamine to phosphatidylcholine. Intracellular localization was visualized by green fluorescent-tagged proteins. Each molecule showed specific localization, and cPLA 2 ␦ translocated from the cytosol to the perinuclear region by calcium-ionophore stimulation. We thus discovered these functional novel cPLA 2 genes, which cluster on murine chromosome 2E5.

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Human Group IVC Phospholipase A2(cPLA2γ)

Cited by 85 publications

References 55 publications

Electrospray Ionization Mass Spectrometry and Exogenous Heavy Isotope-labeled Lipid Species Provide Detailed Information on Aminophospholipid Acyl Chain Remodeling

Electrospray Ionization Mass Spectrometry and Exogenous Heavy Isotope-labeled Lipid Species Provide Detailed Information on Aminophospholipid Acyl Chain Remodeling

Regulatory Mechanism and Physiological Role of Cytosolic Phospholipase A2

Identification of Novel Cytosolic Phospholipase A2s, Murine cPLA2δ, ϵ, and ζ, Which Form a Gene Cluster with cPLA2β

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