PMID- 10455175
OWN - NLM
STAT- MEDLINE
DCOM- 19990930
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 35
DP  - 1999 Aug 27
TI  - Cloning and characterization of novel mouse and human secretory phospholipase
      A(2)s.
PG  - 24973-9
AB  - Mammalian secretory phospholipase A(2)s (sPLA(2)s) are classified into several
      groups according to molecular structure and the localization of intramolecular
      disulfide bridges. Among them, group IIA sPLA(2) has been thought to be one of
      the key enzymes in the pathogenesis of inflammatory diseases owing to its
      augmented expression under various inflammatory conditions. However, in a number 
      of inbred mouse strains, the group IIA sPLA(2) gene is naturally disrupted by a
      frameshift mutation. Here, we report the cloning of a cDNA encoding a novel
      sPLA(2) expressed in the spleen of group IIA sPLA(2)-deficient mouse. We also
      cloned its human homolog and mapped its gene location on chromosome 1p36.12 near 
      the loci of group IIA and V sPLA(2) genes. The human mature sPLA(2) protein
      consists of 125 amino acids (M(r) = 14,500) preceded by a 20-residue prepeptide
      and is most similar to group IIA sPLA(2) with respect to the number and positions
      of cysteine residues as well as overall identity (48%). Based on these structural
      properties, the novel sPLA(2) should be categorized into group II, called group
      IID to follow the already identified IIA to IIC sPLA(2)s. When the cDNA was
      expressed in COS-7 cells, PLA(2) activity preferentially accumulated in the
      culture medium. It is maximally active at neutral to alkaline pH and with 2 mM
      Ca(2+). In assays with individual substrates, L-alpha-1-palmitoyl-2-linoleoyl
      phosphatidylethanolamine was more efficiently hydrolyzed than the other
      phospholipids examined. An RNA blot hybridized with the cDNA exhibited two
      transcripts (2.0 and 1.0 kb) in human spleen, thymus, and colon. The expression
      of a novel sPLA(2) mRNA was elevated in the thymus after treatment with endotoxin
      in rats as well as in group IIA sPLA(2)-deficient mice, suggesting its functional
      role in the progression of the inflammatory process.
FAU - Ishizaki, J
AU  - Ishizaki J
AD  - Shionogi Research Laboratories, Shionogi and Co., Ltd., Sagisu 5-12-4,
      Fukushima-ku, Osaka 553-0002, Japan.
FAU - Suzuki, N
AU  - Suzuki N
FAU - Higashino, K
AU  - Higashino K
FAU - Yokota, Y
AU  - Yokota Y
FAU - Ono, T
AU  - Ono T
FAU - Kawamoto, K
AU  - Kawamoto K
FAU - Fujii, N
AU  - Fujii N
FAU - Arita, H
AU  - Arita H
FAU - Hanasaki, K
AU  - Hanasaki K
LA  - eng
SI  - GENBANK/AF112982
SI  - GENBANK/AF112983
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.1.1.32 (Phospholipases A)
RN  - EC 3.1.1.4 (Group II Phospholipases A2)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - COS Cells
MH  - Calcium/pharmacology
MH  - Chromosome Mapping
MH  - Cloning, Molecular
MH  - Group II Phospholipases A2
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Lipopolysaccharides/pharmacology
MH  - Mice
MH  - Molecular Sequence Data
MH  - Phospholipases A/chemistry/*genetics
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Recombinant Proteins/chemistry
MH  - Sequence Alignment
MH  - Spleen/enzymology
MH  - Substrate Specificity
MH  - Transfection
EDAT- 1999/08/24 00:00
MHDA- 1999/08/24 00:01
CRDT- 1999/08/24 00:00
PHST- 1999/08/24 00:00 [pubmed]
PHST- 1999/08/24 00:01 [medline]
PHST- 1999/08/24 00:00 [entrez]
AID - 10.1074/jbc.274.35.24973 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Aug 27;274(35):24973-9. doi: 10.1074/jbc.274.35.24973.