Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 275, Issue 8, Pages 5785-5793Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.275.8.5785
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Mammalian secretory phospholipase A(2)s (sPLA(2)s) form a family of structurally related enzymes that are involved in a variety of physiological and pathological processes via the release of arachidonic acid from membrane phospholipids or the binding to specific membrane receptors. Here, we report the cloning and characterization of a novel sPLA(2) that is the sixth isoform of the sPLA(2) family found in humans. The novel human mature sPLA(2) consists of 123 amino acids (M-r = 14,000) and is most similar to group IIA sPLA(2) (sPLA(2)-IIA) with respect to the number and positions of cysteine residues as well as overall identity (51%), Therefore, this novel sPLA(2) should be categorized into group II and called group IIE (sPLA(2)-IIE) following the recently identified group IID sPLA(2) (sPLA(2)-IID). The enzymatic properties of recombinant human sPLA(2)-IIE were almost identical to those of sPLA(2)-IIA and IID in terms of Ca2+ requirement, optimal pH, substrate specificity, as well as high susceptibility to the sPLA(2) inhibitor indoxam. Along with the biochemical properties of proteins, genetic and evolutional similarities were also observed among these three types of group II sPLA(2)s as to the chromosomal location of the human gene (1p36) and the exon/intron organization. The expression of sPLA(2)-IIE transcripts in humans was restricted to the brain, heart, lung, and placenta in contrast to broad expression profiles for sPLA(2)-IIA and -IID. In sPLA(2)-IIA-deficient mice, the expression of sPLA(2)-IIE was markedly enhanced in the lung and small intestine upon endotoxin challenge, which contrasted with the reduced expression of sPLA(2)-IID mRNA In situ hybridization analysis revealed elevation of sPLA(2)-IIE mRNA at alveolar macrophage-like cells in the lung of endotoxin-treated mice. These findings suggest a distinct functional role of novel sPLA(2)-IIE in the progression of inflammatory processes.
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