Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lysophosphatidic acid (LPA) is an important lipid mediator that binds to G-protein-coupled receptors of the Edg family, inducing proliferation and migration in many cell lines. Much has been learned about pathways involved in LPA signaling, but the pathways responsible for LPA production remain to be fully resolved. Several potential routes have been proposed for LPA production. One involves the sequential actions of phopholipase D (PLD) and phospholipase A(2) (PLA(2)). Another route involves the sequential actions of PLA(2) and lysophospholipase D (lysoPLD). LysoPLD is defined as an enzyme which hydrolyzes lysophospholipids to produce LPA. Two major forms of lysoPLD, microsomal and extracellular forms, have been reported. A microsomal lysoPLD plays an important role in the metabolism of platelet-activating factor (PAF) because of its preference for alkyl-phospholipids. The extracellular form of lysoPLD coexists with its substrate, lysophosphatidylcholine (LPC), in the extracellular compartment. LysoPLDs purified from the extracellular space have recently been shown to be molecularly identical to autotaxin (ATX). ATX, an enzyme previously known to possess 5'-nucleotide pyrophosphatase and phosphodiesterase (PDE) activities, was subsequently shown to have lysoPLD activity. The unexpected linkage of the extracellular lysoPLD with ATX has raised many interesting questions. The characterization and purification of lysoPLDs are reviewed here.
 ...
PMID:Lysophospholipase D and its role in LPA production. 1521 58

Lysophosphatidic acid (LPA), a potent bioactive phospholipid, induces diverse cellular responses, including cell proliferation, migration, and cytokine release. LPA can be generated intracellularly and extracellularly through multiple synthetic pathways by action of various enzymes, such as phospholipase A(1/2) (PLA(1/2)), phospholipase D (PLD), acylglycerol kinase (AGK), and lysophospholipase D (lysoPLD). Metabolism of LPA is regulated by a family of lipid phosphate phosphatases (LPPs). Significant amounts of LPA have been detected in various biological fluids, including serum, saliva, and bronchoalveolar lavage fluid (BALF). The most significant effects of LPA appear to be through activation of the G-protein-coupled receptors (GPCRs), termed LPA(1-6). LPA regulates gene expression through activation of several transcriptional factors, such as nuclear factor-kappaB (NF-kappaB), AP-1, and C/EBPbeta. In addition to GPCRs, cross-talk between LPA receptors and receptor tyrosine kinases (RTKs) partly regulates LPA-induced intracellular signaling and cellular responses. Airway epithelial cells participate in innate immunity through the release of cytokines, chemokines, lipid mediators, other inflammatory mediators and an increase in barrier function in response to a variety of inhaled stimuli. Expression of LPA receptors has been demonstrated in airway epithelial cells. This review summarizes our recent observations of the role of LPA/LPA-Rs in regulation of airway epithelium, especially in relation to the secretion of pro- and anti-inflammatory mediators and regulation of airway barrier function.
 ...
PMID:Lysophosphatidic acid signaling in airway epithelium: role in airway inflammation and remodeling. 1899 73

Platelet activation initiates an upsurge in polyunsaturated (18:2 and 20:4) lysophosphatidic acid (LPA) production. The biochemical pathway(s) responsible for LPA production during blood clotting are not yet fully understood. Here we describe the purification of a phospholipase A(1) (PLA(1)) from thrombin-activated human platelets using sequential chromatographic steps followed by fluorophosphonate (FP)-biotin affinity labeling and proteomics characterization that identified acyl-protein thioesterase 1 (APT1), also known as lysophospholipase A-I (LYPLA-I; accession code O75608) as a novel PLA(1). Addition of this recombinant PLA(1) significantly increased the production of sn-2-esterified polyunsaturated LPCs and the corresponding LPAs in plasma. We examined the regioisomeric preference of lysophospholipase D/autotaxin (ATX), which is the subsequent step in LPA production. To prevent acyl migration, ether-linked regioisomers of oleyl-sn-glycero-3-phosphocholine (lyso-PAF) were synthesized. ATX preferred the sn-1 to the sn-2 regioisomer of lyso-PAF. We propose the following LPA production pathway in blood: 1) Activated platelets release PLA(1); 2) PLA(1) generates a pool of sn-2 lysophospholipids; 3) These newly generated sn-2 lysophospholipids undergo acyl migration to yield sn-1 lysophospholipids, which are the preferred substrates of ATX; and 4) ATX cleaves the sn-1 lysophospholipids to generate sn-1 LPA species containing predominantly 18:2 and 20:4 fatty acids.
 ...
PMID:The phospholipase A1 activity of lysophospholipase A-I links platelet activation to LPA production during blood coagulation. 2139 52

Lysophospholipids (LPLs), such as lysophosphatidic acid (LPA), sphingosine 1-phosphate (S1P), and lysophosphatidylserine (LysoPS), are attracting attention as second-generation lipid mediators. In our laboratory, the functional roles of these lipid mediators and the mechanisms by which the levels of these mediators are regulated in vivo have been studied. Based on these studies, the clinical introduction of assays for LPLs and related proteins has been pursued and will be described in this review. Although assays of these lipids themselves are possible, autotaxin (ATX), apolipoprotein M (ApoM), and phosphatidylserine-specific phospholipase A1 (PS-PLA1) are more promising as alternate biomarkers for LPA, S1P, and LysoPS, respectively. Presently, ATX, which produces LPA through its lysophospholipase D activity, has been shown to be a useful laboratory test for the diagnosis and staging of liver fibrosis, whereas PS-PLA1 and ApoM are considered to be promising clinical markers reflecting the in vivo actions induced by LysoPS and S1P.
 ...
PMID:Lysophospholipids in laboratory medicine. 3054 65