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PMID:17293613

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Citation

Ghosh, M, Loper, R, Ghomashchi, F, Tucker, DE, Bonventre, JV, Gelb, MH and Leslie, CC (2007) Function, activity, and membrane targeting of cytosolic phospholipase A(2)zeta in mouse lung fibroblasts. J. Biol. Chem. 282:11676-86

Abstract

Group IVA cytosolic phospholipase A(2) (cPLA(2)alpha) initiates eicosanoid production; however, this pathway is not completely ablated in cPLA(2)alpha(-/-) lung fibroblasts stimulated with A23187 or serum. cPLA(2)alpha(+/+) fibroblasts preferentially released arachidonic acid, but A23187-stimulated cPLA(2)alpha(-/-) fibroblasts nonspecifically released multiple fatty acids. Arachidonic acid release from cPLA(2) alpha(-/-) fibroblasts was inhibited by the cPLA(2)alpha inhibitors pyrrolidine-2 (IC(50), 0.03 microM) and Wyeth-1 (IC(50), 0.1 microM), implicating another C2 domain-containing group IV PLA(2). cPLA(2) alpha(-/-) fibroblasts contain cPLA(2)beta and cPLA(2)zeta but not cPLA(2)epsilon or cPLA(2)delta. Purified cPLA(2)zeta exhibited much higher lysophospholipase and PLA(2) activity than cPLA(2)beta and was potently inhibited by pyrrolidine-2 and Wyeth-1, which did not inhibit cPLA(2)beta. In contrast to cPLA(2)beta, cPLA(2)zeta expressed in Sf9 cells mediated A23187-induced arachidonic acid release, which was inhibited by pyrrolidine-2 and Wyeth-1. cPLA(2)zeta exhibits specific activity, inhibitor sensitivity, and low micromolar calcium dependence similar to cPLA(2)alpha and has been identified as the PLA(2) responsible for calcium-induced fatty acid release and prostaglandin E(2) production from cPLA(2) alpha(-/-) lung fibroblasts. In response to ionomycin, EGFP-cPLA(2)zeta translocated to ruffles and dynamic vesicular structures, whereas EGFP-cPLA(2)alpha translocated to the Golgi and endoplasmic reticulum, suggesting distinct mechanisms of regulation for the two enzymes.

Links

PubMed PMC2678067 Online version:10.1074/jbc.M608458200

Keywords

Amino Acid Sequence; Animals; Arachidonic Acid/metabolism; Cytosol/metabolism; Endoplasmic Reticulum/metabolism; Fibroblasts/metabolism; Golgi Apparatus/metabolism; Group IV Phospholipases A2; Insects; Lung/metabolism; Mice; Molecular Sequence Data; Phosphoinositide Phospholipase C; Phospholipases A/genetics; Phospholipases A/metabolism; Phospholipases A/physiology; Protein Transport; Sequence Homology, Amino Acid; Type C Phospholipases/metabolism; Type C Phospholipases/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:TGFB1

acts_upstream_of_or_within

GO:0010628: positive regulation of gene expression

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(MGI:MGI:97798)

Seeded From UniProt

complete

MOUSE:PA24B

enables

GO:0004622: lysophospholipase activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:PA24B

enables

GO:0004623: phospholipase A2 activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:PA24A

located_in

GO:0005783: endoplasmic reticulum

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PA24A

located_in

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000057)

Seeded From UniProt

complete

MOUSE:PA24A

located_in

GO:0005794: Golgi apparatus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PA24A

acts_upstream_of_or_within

GO:0050482: arachidonic acid secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:PA24A

acts_upstream_of_or_within

GO:0046456: icosanoid biosynthetic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:PA24A

acts_upstream_of_or_within

GO:0071236: cellular response to antibiotic

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PA24F

acts_upstream_of_or_within

GO:0001516: prostaglandin biosynthetic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PA24F

located_in

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000057)

Seeded From UniProt

complete

MOUSE:PA24F

acts_upstream_of_or_within

GO:0015908: fatty acid transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PA24F

enables

GO:0004622: lysophospholipase activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:PA24F

enables

GO:0004623: phospholipase A2 activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:PA24F

located_in

GO:0032587: ruffle membrane

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000057)

Seeded From UniProt

complete

MOUSE:PA24F

located_in

GO:0031982: vesicle

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000057)

Seeded From UniProt

complete

MOUSE:PA24F

enables

GO:0047498: calcium-dependent phospholipase A2 activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:PA24F

acts_upstream_of_or_within

GO:0050482: arachidonic acid secretion

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PA24F

acts_upstream_of_or_within

GO:0071407: cellular response to organic cyclic compound

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PA24F

acts_upstream_of_or_within

GO:0071236: cellular response to antibiotic

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TGFB1

acts_upstream_of_or_within

GO:0010628: positive regulation of gene expression

ECO:0000314: direct assay evidence used in manual assertion

P

has_regulation_target:(MGI:MGI:97798)

Seeded From UniProt

complete


See also

References

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