Structure and function of phosphatidylserine-specific phospholipase A1

Aoki, Junken; Nagai, Yuki; Hosono, Hiroyuki; Inoue, Kazuhide; Arai, Hiroyuki

doi:10.1016/s1388-1981(02)00134-8

Cited by 115 publications

(88 citation statements)

References 29 publications

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“…Furthermore, lyso-PA was unable to induce calcium flux, suggesting that the presence of a bulky head group is a requirement for G2A signaling (see below). Additionally, little is known of lyso-PL degradation or reacylation, which may be head group specific (52)(53)(54)(55) and may also alter biological activity in diverse in vitro and in vivo systems.…”

Section: Discussionmentioning

confidence: 99%

Lysophospholipids of Different Classes Mobilize Neutrophil Secretory Vesicles and Induce Redundant Signaling through G2A

Frasch

Berry²,

Murphy³

et al. 2007

The Journal of Immunology

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Lysophosphatidylcholine has been shown to enhance neutrophil functions through a mechanism involving the G protein-coupled receptor G2A. Recent data support an indirect effect of lysophosphatidylcholine on G2A rather than direct ligand binding. These observations prompted the hypothesis that other lysophospholipids (lyso-PLs) may also signal for human neutrophil activation through G2A. To this end, 1-oleoyl-2-hydroxy-sn-glycero-3-[phospho-l-choline], but also C18:1/OH lyso-PLs bearing the phosphoserine and phosphoethanolamine head groups, presented on albumin, were shown to signal for calcium flux in a self- and cross-desensitizing manner, implicating a single receptor. Blocking Abs to G2A inhibited calcium signaling by all three lyso-PLs. Furthermore, inhibition by both pertussis toxin and U-73122 established signaling via the Gαi/phospholipase C pathway for calcium mobilization. Altered plasma membrane localization of G2A has been hypothesized to facilitate signaling. Accordingly, an increase in detectable G2A was demonstrated by 1 min after lyso-PL stimulation and was followed by visible patching of the receptor. Western blotting showed that G2A resides in the plasma membrane/secretory vesicle fraction and not in neutrophil primary, secondary, or tertiary granules. Enhanced detection of G2A induced by lyso-PLs was paralleled by enhanced detection of CD45, confirming mobilization of the labile secretory vesicle pool. Together, these data show that lyso-PLs bearing various head groups redundantly mobilize G2A latent within secretory vesicles and result in G2A receptor/Gαi/phospholipase C signaling for calcium flux in neutrophils.

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Section: Discussionmentioning

confidence: 99%

Lysophospholipids of Different Classes Mobilize Neutrophil Secretory Vesicles and Induce Redundant Signaling through G2A

Frasch

Berry²,

Murphy³

et al. 2007

The Journal of Immunology

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“…: The abbreviations used are: GPCR, G protein-coupled receptor; DTH, delayed type hypersensitivity; hiCap, heat-inactivated acapsular C. neoformans serotype D strain CAP67; lyso-PS, lyso-phosphatidylserine; P-lyso-PS, 1-palmitoyl-lyso-phosphatidylserine; qPCR, quantitative real time PCR analysis; S-lyso-PS, 1-stearyl-lyso-phosphatidylserine; TM, transmembrane region; mBSA, methylated BSA. pholipases A 1 and A 2 when apoptotic cells expose phosphatidylserine on their surface to these phospholipases (17,18). lyso-PS is a potent activator of histamine release from mast cells (19).…”

Section: G Protein-coupled Receptors (Gpcr)mentioning

confidence: 99%

“…Specifically, GPR34 was shown to be activated by lyso-phosphatidylserine (lyso-PS) in vitro. lyso-PS is generated by hydrolysis of membrane lipids through phos-pholipases A 1 and A 2 when apoptotic cells expose phosphatidylserine on their surface to these phospholipases (17,18). lyso-PS is a potent activator of histamine release from mast cells (19).…”

mentioning

confidence: 99%

Altered Immune Response in Mice Deficient for the G Protein-coupled Receptor GPR34

Liebscher¹,

Müller

Teupser

et al. 2011

Journal of Biological Chemistry

103

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The X-chromosomal GPR34 gene encodes an orphan G i protein-coupled receptor that is highly conserved among vertebrates. To evaluate the physiological relevance of GPR34, we generated a GPR34-deficient mouse line. GPR34-deficient mice were vital, reproduced normally, and showed no gross abnormalities in anatomical, histological, laboratory chemistry, or behavioral investigations under standard housing. Because GPR34 is highly expressed in mononuclear cells of the immune system, mice were specifically tested for altered functions of these cell types. Following immunization with methylated BSA, the number of granulocytes and macrophages in spleens was significantly lower in GPR34-deficient mice as in wild-type mice. GPR34-deficient mice showed significantly increased paw swelling in the delayed type hypersensitivity test and higher pathogen burden in extrapulmonary tissues after pulmonary infection with Cryptococcus neoformans compared with wild-type mice. The findings in delayed type hypersensitivity and infection tests were accompanied by significantly different basal and stimulated TNF-␣, GM-CSF, and IFN-␥ levels in GPR34-deficient animals. Our data point toward a functional role of GPR34 in the cellular response to immunological challenges. G protein-coupled receptors (GPCR)2 form the largest gene family among transmembrane receptors, including more than 900 genes in humans and other mammals (1). A great number of stimuli, such as light, hormones, neurotransmitters, peptides, and nucleotides, activate the distinct receptors. Nonodorant receptors form about one-third of the GPCR repertoire. Although more than 200 non-odorant GPCR have been assigned to specific agonists and functions, about 155 socalled "orphan" GPCR (2) await identification of their physiological relevance. The importance of GPCR in controlling almost every physiological function makes this receptor family the most frequently used target for therapeutic drugs. Therefore, unveiling the function of orphan GPCR is a central issue in academic and industrial research.Among the five structurally different GPCR families (1, 3), the rhodopsin-like receptors form the largest in humans and other vertebrates. The rhodopsin-like family is divided further into subfamilies and groups. The P2Y 12 -like receptor group includes the ADP receptors P2Y 12 and P2Y 13 , the UDP-glucose receptor P2Y 14 , and the orphan receptors GPR87, GPR82, and GPR34 (4). Apart from the ADP receptor P2Y 12 , which has a central role in platelet aggregation and is the therapeutic target of clopidogrel (5, 6), very little is known about the function of the other members of this group.GPR34, an orphan receptor of the P2Y 12 -like receptor group, was first discovered by mining GenBank TM for novel GPCR sequences and homology cloning and has been assigned to the human X chromosome (7,8). Phylogenetic studies revealed that GPR34 has been highly conserved over the past 450 million years of vertebrate evolution, and no GPR34-deficient vertebrate has been identified yet (9). To date, there i...

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“…Phospholipase (PL) A 1 and PLA 2 catalyze the esterolytic cleavage at the sn-1 or sn-2 position of glycerophospholipids, respectively, resulting in the formation of FFAs and lysophospholipids (1)(2)(3)(4)(5). Arachidonic acid released by PLA 2 is further converted into various bioactive eicosanoids (6), whereas lysophospholipids serve as lipid mediators (for example, lysophosphatidic acid, lysophosphatidylserine, and lysophosphatidylinositol) (7)(8)(9)(10) or precursors for lipid mediators (platelet-activating factor) (11).…”

mentioning

confidence: 99%

“…As for PLA 2 , more than 20 isozymes have been cloned and characterized in mammals, and their physiological functions have been extensively analyzed (1)(2)(3). On the other hand, at least 9 isozymes of PLA 1 have been cloned (4,5). Each isozyme is classified into a subgroup, depending on its primary structure, extracellular or intracellular localization, Ca 21 dependency, and specific inhibition by synthetic compounds.…”

mentioning

confidence: 99%

The tumor suppressor gene H-Rev107 functions as a novel Ca2+-independent cytosolic phospholipase A1/2 of the thiol hydrolase type

Uyama

Morishita

Jin

et al. 2009

Journal of Lipid Research

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H-Rev107 is a protein that was previously cloned as a negative regulator of proto-oncogene Ras and classified as a class II tumor suppressor. Its structural similarity to lecithin retinol acyltransferase and Ca 21 -independent phosphatidylethanolamine (PE) N-acyltransferase led us to analyze H-Rev107 as an enzyme involved in phospholipid metabolism. Here, we show that recombinant H-Rev107s from rat, human, and mouse possess phospholipase (PL) A 1 or A 2 activity toward phosphatidylcholine (PC). Further examination with purified recombinant protein revealed that H-Rev107 functions as a cytosolic Ca 21 -independent PLA 1/2 for PC and PE with higher PLA 1 activity than PLA 2 activity. Dithiothreitol and iodoacetic acid exhibited stimulatory and inhibitory effects, respectively. Histidine-21 and cysteine-111 of rat H-Rev107 were presumed to form a catalytic dyad based on database analysis, and their single mutants were totally inactive. These results suggested that H-Rev107 is a hydrolase of the thiol type. The N-terminal proline-rich and C-terminal hydrophobic domains of H-Rev107 were earlier reported to be responsible for the regulation of cell proliferation. Analysis of deletion mutants indicated that these domains are also catalytically essential, suggesting relevance of the catalytic activity to the anti-proliferative activity.-Uyama, T., J.

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Structure and function of phosphatidylserine-specific phospholipase A1

Cited by 115 publications

References 29 publications

Lysophospholipids of Different Classes Mobilize Neutrophil Secretory Vesicles and Induce Redundant Signaling through G2A

Lysophospholipids of Different Classes Mobilize Neutrophil Secretory Vesicles and Induce Redundant Signaling through G2A

Altered Immune Response in Mice Deficient for the G Protein-coupled Receptor GPR34

The tumor suppressor gene H-Rev107 functions as a novel Ca2+-independent cytosolic phospholipase A1/2 of the thiol hydrolase type

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