PMID- 10336645
OWN - NLM
STAT- MEDLINE
DCOM- 19990624
LR  - 20190620
IS  - 0014-2956 (Print)
IS  - 0014-2956 (Linking)
VI  - 262
IP  - 2
DP  - 1999 Jun
TI  - The human calcium-independent phospholipase A2 gene multiple enzymes with
      distinct properties from a single gene.
PG  - 575-85
AB  - Recently, we reported the human 88-kDa calcium-independent phospholipase A2
      (iPLA2) cDNA sequence, as well as extensive alternative splicing of the iPLA2
      mRNA. In this report we identified the gene coding for iPLA2, which was localized
      on chromosome 22q13.1. The gene consists of at least 17 exons spanning > 69 kb.
      Based on the iPLA2 gene organization the splice variants can be explained. The
      putative promotor for the iPLA2 gene lacks a TATA-box and contains a CpG island
      as well as several potential Sp-1-binding sites. Furthermore, the 5'-flanking
      region also contains one medium reiteration frequency repeat (MER53) and an Alu
      repetitive sequence. Northern blot analysis of iPLA2 mRNA in various human
      tissues demonstrated tissue-specific expression of four distinct iPLA2
      transcripts. The native human 3.2-kb iPLA2 transcript was predominantly expressed
      in heart, brain, skeletal muscle, prostate, testis, thyroid and spinal cord, and 
      to a lesser extent in peripheral blood leucocytes, stomach, trachea and bone
      marrow. Studies on the subcellular localization of the native iPLA2 protein were 
      performed in COS-7 cells overexpressing this enzyme. The cytosolic fraction of
      untransfected and cells overexpressing iPLA2 contained equal amounts of
      calcium-independent PLA2 activity. However, the membrane fraction displayed a
      5.5-fold increased activity in iPLA2 overexpressing cells. This increased
      calcium-independent PLA2 activity correlated with the presence of iPLA2
      immunoreactive protein in the membrane fraction, indicating that this form of
      iPLA2 protein was membrane associated. Studies of iPLA2 in rat vascular smooth
      muscle cells verified the membrane association of this form of iPLA2. The major
      difference between this form of iPLA2 enzyme and the soluble forms of iPLA2
      studied previously is the presence of 54 additional amino acid residues derived
      from exon 9. We suggest that the addition of these 54 amino acids leads to a
      membrane-associated protein. In summary, these results demonstrate that
      alternative splicing of the human iPLA2 transcript generates multiple iPLA2
      isoforms with distinct tissue distribution and cellular localization.
FAU - Larsson Forsell, P K
AU  - Larsson Forsell PK
AD  - Department of Medical Biochemistry, Karolinska Institutet, Stockholm, Sweden.
FAU - Kennedy, B P
AU  - Kennedy BP
FAU - Claesson, H E
AU  - Claesson HE
LA  - eng
SI  - GENBANK/AF115252
SI  - GENBANK/AF117676
SI  - GENBANK/AF117677
SI  - GENBANK/AF117678
SI  - GENBANK/AF117679
SI  - GENBANK/AF117680
SI  - GENBANK/AF117681
SI  - GENBANK/AF117682
SI  - GENBANK/AF117683
SI  - GENBANK/AF117684
SI  - GENBANK/AF117685
SI  - GENBANK/AF117686
SI  - GENBANK/AF117687
SI  - GENBANK/AF117688
SI  - GENBANK/AF117689
SI  - GENBANK/AF117690
SI  - GENBANK/AF117691
SI  - GENBANK/AF117692
SI  - GENBANK/AH007709
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Biochem
JT  - European journal of biochemistry
JID - 0107600
RN  - 0 (Isoenzymes)
RN  - 0 (RNA, Messenger)
RN  - 9007-49-2 (DNA)
RN  - EC 3.1.1.32 (Phospholipases A)
RN  - EC 3.1.1.4 (Phospholipases A2)
SB  - IM
MH  - Alternative Splicing
MH  - Animals
MH  - Base Sequence
MH  - Blotting, Northern
MH  - COS Cells
MH  - DNA
MH  - Exons
MH  - Humans
MH  - Introns
MH  - Isoenzymes/*genetics/metabolism
MH  - Molecular Sequence Data
MH  - Phospholipases A/*genetics/metabolism
MH  - Phospholipases A2
MH  - RNA, Messenger/genetics
MH  - Rats
MH  - Subcellular Fractions/enzymology
EDAT- 1999/05/21 00:00
MHDA- 1999/05/21 00:01
CRDT- 1999/05/21 00:00
PHST- 1999/05/21 00:00 [pubmed]
PHST- 1999/05/21 00:01 [medline]
PHST- 1999/05/21 00:00 [entrez]
AID - 10.1046/j.1432-1327.1999.00418.x [doi]
PST - ppublish
SO  - Eur J Biochem. 1999 Jun;262(2):575-85. doi: 10.1046/j.1432-1327.1999.00418.x.