Cytosolic phospholipase A2: physiological function and role in disease

The group IV phospholipase A2 (PLA2) family is comprised of six intracellular enzymes (GIVA, -B, -C, -D, -E, and -F) commonly referred to as cytosolic PLA2 (cPLA2)α, -β, -γ, -δ, -ε, and -ζ. They contain a Ser-Asp catalytic dyad and all except cPLA2γ have a C2 domain, but differences in their catalyt...

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Published inJournal of lipid research Vol. 56; no. 8; pp. 1386 - 1402
Main Author Leslie, Christina C.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.08.2015
The American Society for Biochemistry and Molecular Biology
Elsevier
SeriesThematic Review Series: Phospholipases: Central Role in Lipid Signaling and Disease
Subjects
Animals
arachidonic acid
calcium
cyclooxygenase
Disease
Golgi apparatus
Humans
inflammation
leukotrienes
lipoxygenase
Phospholipases A2, Cytosolic - chemistry
Phospholipases A2, Cytosolic - metabolism
prostaglandins
protein kinases/MAP kinase
Thematic Review Series
arachidonic acid
lipoxygenase
calcium
inflammation
protein kinases/MAP kinase
cyclooxygenase
prostaglandins
leukotrienes
Golgi apparatus
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Abstract The group IV phospholipase A2 (PLA2) family is comprised of six intracellular enzymes (GIVA, -B, -C, -D, -E, and -F) commonly referred to as cytosolic PLA2 (cPLA2)α, -β, -γ, -δ, -ε, and -ζ. They contain a Ser-Asp catalytic dyad and all except cPLA2γ have a C2 domain, but differences in their catalytic activities and subcellular localization suggest unique regulation and function. With the exception of cPLA2α, the focus of this review, little is known about the in vivo function of group IV enzymes. cPLA2α catalyzes the hydrolysis of phospholipids to arachidonic acid and lysophospholipids that are precursors of numerous bioactive lipids. The regulation of cPLA2α is complex, involving transcriptional and posttranslational processes, particularly increases in calcium and phosphorylation. cPLA2α is a highly conserved widely expressed enzyme that promotes lipid mediator production in human and rodent cells from a variety of tissues. The diverse bioactive lipids produced as a result of cPLA2α activation regulate normal physiological processes and disease pathogenesis in many organ systems, as shown using cPLA2α KO mice. However, humans recently identified with cPLA2α deficiency exhibit more pronounced effects on health than observed in mice lacking cPLA2α, indicating that much remains to be learned about this interesting enzyme.
AbstractList The group IV phospholipase A2 (PLA2) family is comprised of six intracellular enzymes (GIVA, -B, -C, -D, -E, and -F) commonly referred to as cytosolic PLA2 (cPLA2)α, -β, -γ, -δ, -ε, and -ζ. They contain a Ser-Asp catalytic dyad and all except cPLA2γ have a C2 domain, but differences in their catalytic activities and subcellular localization suggest unique regulation and function. With the exception of cPLA2α, the focus of this review, little is known about the in vivo function of group IV enzymes. cPLA2α catalyzes the hydrolysis of phospholipids to arachidonic acid and lysophospholipids that are precursors of numerous bioactive lipids. The regulation of cPLA2α is complex, involving transcriptional and posttranslational processes, particularly increases in calcium and phosphorylation. cPLA2α is a highly conserved widely expressed enzyme that promotes lipid mediator production in human and rodent cells from a variety of tissues. The diverse bioactive lipids produced as a result of cPLA2α activation regulate normal physiological processes and disease pathogenesis in many organ systems, as shown using cPLA2α KO mice. However, humans recently identified with cPLA2α deficiency exhibit more pronounced effects on health than observed in mice lacking cPLA2α, indicating that much remains to be learned about this interesting enzyme.
The group IV phospholipase A 2 (PLA 2 ) family is comprised of six intracellular enzymes (GIVA, -B, -C, -D, -E, and -F) commonly referred to as cytosolic PLA 2 (cPLA 2 )α, -β, -γ, -δ, -ε, and -ζ. They contain a Ser-Asp catalytic dyad and all except cPLA 2 γ have a C2 domain, but differences in their catalytic activities and subcellular localization suggest unique regulation and function. With the exception of cPLA 2 α, the focus of this review, little is known about the in vivo function of group IV enzymes. cPLA 2 α catalyzes the hydrolysis of phospholipids to arachidonic acid and lysophospholipids that are precursors of numerous bioactive lipids. The regulation of cPLA 2 α is complex, involving transcriptional and posttranslational processes, particularly increases in calcium and phosphorylation. cPLA 2 α is a highly conserved widely expressed enzyme that promotes lipid mediator production in human and rodent cells from a variety of tissues. The diverse bioactive lipids produced as a result of cPLA 2 α activation regulate normal physiological processes and disease pathogenesis in many organ systems, as shown using cPLA 2 α KO mice. However, humans recently identified with cPLA 2 α deficiency exhibit more pronounced effects on health than observed in mice lacking cPLA 2 α, indicating that much remains to be learned about this interesting enzyme.
Author Leslie, Christina C.
Author_xml – sequence: 1
  givenname: Christina C.
  surname: Leslie
  fullname: Leslie, Christina C.
  email: lesliec@njealth.org
  organization: Department of Pediatrics, National Jewish Health, Denver, CO 80206; and Departments of Pathology and Pharmacology, University of Colorado Denver, Aurora, CO 80045
BackLink https://www.ncbi.nlm.nih.gov/pubmed/25838312$$D View this record in MEDLINE/PubMed
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Keywords arachidonic acid
lipoxygenase
calcium
inflammation
protein kinases/MAP kinase
cyclooxygenase
prostaglandins
leukotrienes
Golgi apparatus
Language English
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Snippet The group IV phospholipase A2 (PLA2) family is comprised of six intracellular enzymes (GIVA, -B, -C, -D, -E, and -F) commonly referred to as cytosolic PLA2...
The group IV phospholipase A 2 (PLA 2 ) family is comprised of six intracellular enzymes (GIVA, -B, -C, -D, -E, and -F) commonly referred to as cytosolic PLA 2...
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SubjectTerms Animals
arachidonic acid
calcium
cyclooxygenase
Disease
Golgi apparatus
Humans
inflammation
leukotrienes
lipoxygenase
Phospholipases A2, Cytosolic - chemistry
Phospholipases A2, Cytosolic - metabolism
prostaglandins
protein kinases/MAP kinase
Thematic Review Series
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Title Cytosolic phospholipase A2: physiological function and role in disease
URI https://dx.doi.org/10.1194/jlr.R057588
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