Cloning, Chromosomal Mapping, and Expression of a Novel Human Secretory Phospholipase A2

Cupillard, Lionel; Koumanov, Kamen; Matteï, Marie‐Geneviève; Lazdunski, Michel; Lambeau, Gérard

doi:10.1074/jbc.272.25.15745

Cited by 247 publications

(266 citation statements)

References 89 publications

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“…Furthermore, analysis by RT-PCR with commercial human tissue cDNA panels indicates a pattern of hGXII expression that is Cloning of Human Group XII sPLA 2 39825 consistent with the Northern blot data and additionally shows that this sPLA 2 is strongly expressed in pancreas and weakly in ovaries, testis, and prostate (not shown). The pattern of expression of hGXII thus appears distinct from that of other known human sPLA 2 s (16,19,22), 3 suggesting specific function(s) for this novel sPLA 2 .…”

Section: Cloning Of Human Group XII Spla 2 39824mentioning

confidence: 84%

“…Recombinant hGXII was found to be a catalytically active sPLA 2 when assayed with the radiolabeled E. coli membrane assay (16) and with POPG, POPS, and POPC vesicles using the fatty acid-binding protein assay (17). As shown in Fig.…”

Section: Cloning Of Human Group XII Spla 2 39824mentioning

confidence: 92%

“…In the last few years, six mouse and five human sPLA 2 s structurally related to GIB and GIIA sPLA 2 s (mGIIC, hGIID, mGIID, hGIIE, mGIIE, mGIIF, hGIIF, hGV, mGV, hGX, and mGX) 2 have been identified (15)(16)(17)(18)(19)(20). 3 All of these group I/II/V/X sPLA 2 s have similar primary structures, including identical catalytic site residues and partially overlapping sets of disulfides (21).…”

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confidence: 99%

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Cloning and Recombinant Expression of a Structurally Novel Human Secreted Phospholipase A2

Gelb¹,

Valentin²,

Ghomashchi³

et al. 2000

Journal of Biological Chemistry

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158

152

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Mammals contain a diverse set of secreted phospholipases A 2 (sPLA 2 s) that liberate arachidonic acid from phospholipids for the production of eicosanoids and exert a variety of physiological and pathological effects. We report the cloning, recombinant expression, and kinetic properties of a novel human sPLA 2 that defines a new structural class of sPLA 2 s called group XII. The human group XII (hGXII) cDNA contains a putative signal peptide of 22 residues followed by a mature protein of 167 amino acids that displays homology to all known sPLA 2 s only over a short stretch of amino acids in the active site region. Northern blot and reverse transcription-polymerase chain reaction analyses show that the tissue distribution of hGXII is distinct from the other human sPLA 2 s with strong expression in heart, skeletal muscle, kidney, and pancreas and weaker expression in brain, liver, small intestine, lung, placenta, ovaries, testis, and prostate. Catalytically active hGXII was produced in Escherichia coli and shown to be Ca 2؉ -dependent despite the fact that it is predicted to have an unusual Ca 2؉ -binding loop. Similar to the previously characterized mouse group IIE sPLA 2 s, the specific activity of hGXII is low in comparison to that of other mammalian sPLA 2 , suggesting that hGXII could have novel functions that are independent of its phospholipase A 2 activity.

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Section: Cloning Of Human Group XII Spla 2 39824mentioning

confidence: 84%

Section: Cloning Of Human Group XII Spla 2 39824mentioning

confidence: 92%

mentioning

confidence: 99%

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Cloning and Recombinant Expression of a Structurally Novel Human Secreted Phospholipase A2

Gelb¹,

Valentin²,

Ghomashchi³

et al. 2000

Journal of Biological Chemistry

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158

152

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“…The sPLA 2 s form a growing family of enzymes that catalyze the hydrolysis of the sn-2 ester bond of glycerophospholipids, leading to the production of free fatty acids and lysophospholipids that serve as precursors for a variety of lipid-derived mediators involved in numerous biological activities (5,6). To date, 10 different sPLA 2 s, referred to as groups IB, IIA, IIC, IID, IIE, IIF, III, V, X, and XII, have been characterized in mammals (7)(8)(9)(10)(11)(12). Of particular interest, levels of sPLA 2 activity in bronchoalveolar lavage fluids (BALF) of patients with ARDS often correlate positively with the severity of the disease (13).…”

Section: Inhibitory Effects Of Surfactant Protein a On Surfactant Phomentioning

confidence: 99%

Inhibitory Effects of Surfactant Protein A on Surfactant Phospholipid Hydrolysis by Secreted Phospholipases A2

Chabot

Koumanov

Lambeau

et al. 2003

The Journal of Immunology

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Hydrolysis of surfactant phospholipids by secreted phospholipases A2 (sPLA2) contributes to surfactant dysfunction in acute respiratory distress syndrome. The present study demonstrates that sPLA2-IIA, sPLA2-V, and sPLA2-X efficiently hydrolyze surfactant phospholipids in vitro. In contrast, sPLA2-IIC, -IID, -IIE, and -IIF have no effect. Since purified surfactant protein A (SP-A) has been shown to inhibit sPLA2-IIA activity, we investigated the in vitro effect of SP-A on the other active sPLA2 and the consequences of sPLA2-IIA inhibition by SP-A on surfactant phospholipid hydrolysis. SP-A inhibits sPLA2-X activity, but fails to interfere with that of sPLA2-V. Moreover, in vitro inhibition of sPLA2-IIA-induces surfactant phospholipid hydrolysis correlates with the concentration of SP-A in surfactant. Intratracheal administration of sPLA2-IIA to mice causes hydrolysis of surfactant phosphatidylglycerol. Interestingly, such hydrolysis is significantly higher for SP-A gene-targeted mice, showing the in vivo inhibitory effect of SP-A on sPLA2-IIA activity. Administration of sPLA2-IIA also induces respiratory distress, which is more pronounced in SP-A gene-targeted mice than in wild-type mice. We conclude that SP-A inhibits sPLA2 activity, which may play a protective role by maintaining surfactant integrity during lung injury.

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“…Based on amino acid sequences, 10 groups of PLA 2 s have been identified, including eight from mammals (4,5). The human group IIa secreted PLA 2 (hIIa-PLA2) is secreted from a number of activated cells including platelets (6), whereas the macrophage-like cell line P3881 secretes a related enzyme, the recently discovered group V PLA 2 (7,8).…”

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confidence: 99%

Action of Human Group IIa Secreted Phospholipase A2on Cell Membranes

Koduri¹,

Baker²,

Snitko³

et al. 1998

Journal of Biological Chemistry

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Human group IIa phospholipase A 2 (hIIa-PLA2) is a highly basic protein that is secreted from a number of cells during inflammation and may play a role in arachidonate liberation and in destruction of invading bacteria. It has been proposed that rodent group IIa PLA 2 is anchored to cell surfaces via attachment to heparan sulfate proteoglycan and that this interaction facilitates lipolysis. hIIa-PLA2 contains 13 lysines, 2 histidines, and 10 arginines that fall into 10 clusters. A panel of 26 hIIa-PLA2 mutants were prepared in which 1-4 basic residues in each cluster were changed to glutamate or aspartate (charge reversal). A detailed analysis of the affinities of these mutants for anionic vesicles and for heparin and heparan sulfate in vitro and of the specific activities of these proteins for hydrolysis of vesicles in vitro and of living cell membranes reveal the following trends: 1) the affinity of hIIa-PLA2 for heparin and heparan sulfate is modulated not by a highly localized site of basic residues but by diffuse sites that partially overlap with the interfacial binding site. In contrast, only those residues on the interfacial binding site of hIIa-PLA2 are involved in binding to membranes; 2) the relative ability of these mutants to hydrolyze cellular phospholipids when enzymes were added exogenously to CHO-K1, NIH-3T3, and RAW 264.7 cells correlates with their relative in vitro affinity for vesicles and not with their affinity for heparin and heparan sulfate. 3) The rates of exogenous hIIa-PLA2-catalyzed fatty acid release from wild type CHO-K1 cells and two mutant lines, one lacking glycosaminoglycan and one lacking heparan sulfate, were similar. Thus basic residues that modulate interfacial binding are important for plasma membrane fatty acid release by exogenously added hIIa-PLA2. Binding of hIIa-PLA2 to cell surface heparan sulfate does not modulate plasma membrane phospholipid hydrolysis by exogenously added hIIa-PLA2.

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Cloning, Chromosomal Mapping, and Expression of a Novel Human Secretory Phospholipase A2

Cited by 247 publications

References 89 publications

Cloning and Recombinant Expression of a Structurally Novel Human Secreted Phospholipase A2

Cloning and Recombinant Expression of a Structurally Novel Human Secreted Phospholipase A2

Inhibitory Effects of Surfactant Protein A on Surfactant Phospholipid Hydrolysis by Secreted Phospholipases A2

Action of Human Group IIa Secreted Phospholipase A2on Cell Membranes

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