PMID- 10085124
OWN - NLM
STAT- MEDLINE
DCOM- 19990429
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 13
DP  - 1999 Mar 26
TI  - Molecular cloning of two new human paralogs of 85-kDa cytosolic phospholipase A2.
PG  - 8823-31
AB  - Two new cloned human cDNAs encode paralogs of the 85-kDa cytosolic phospholipase 
      A2 (cPLA2). We propose to call these cPLA2beta (114 kDa) and cPLA2gamma (61 kDa),
      giving the name cPLA2alpha to the well known 85-kDa enzyme. cPLA2beta mRNA is
      expressed more highly in cerebellum and pancreas and cPLA2gamma more highly in
      cardiac and skeletal muscle. Sequence-tagged site mapping places cPLA2beta on
      chromosome 15 in a region near a phosphoinositol bisphosphate phosphatase. The
      mRNA for cPLA2beta is spliced only at a very low level, and Northern blots in 24 
      tissues show exclusively the unspliced form. cPLA2beta has much lower activity on
      2-arachidonoyl-phosphatidylcholine liposomes than either of the other two
      enzymes. Its sequence contains a histidine motif characteristic of the catalytic 
      center of caspase proteases of the apoptotic cascade but no region characteristic
      of the catalytic cysteine. Sequence-tagged site mapping places cPLA2gamma on
      chromosome 19 near calmodulin. cPLA2gamma lacks the C2 domain, which gives
      cPLA2alpha its Ca2+ sensitivity, and accordingly cPLA2gamma has no dependence
      upon calcium, although cPLA2beta does. cPLA2gamma contains a prenyl group-binding
      site motif and appears to be largely membrane-bound. cPLA2alpha residues
      activated by phosphorylation do not appear to be well conserved in either new
      enzyme. In contrast, all three previously known catalytic residues, as well as
      one additional essential arginine, Arg-566 in cPLA2alpha, are conserved in both
      new enzyme sequences. Mutagenesis shows strong dependence on these residues for
      catalytic activity of all three enzymes.
FAU - Pickard, R T
AU  - Pickard RT
AD  - Lilly Research Laboratory, Indianapolis, Indiana 46285, USA.
FAU - Strifler, B A
AU  - Strifler BA
FAU - Kramer, R M
AU  - Kramer RM
FAU - Sharp, J D
AU  - Sharp JD
LA  - eng
SI  - GENBANK/AF065214
SI  - GENBANK/AF065215
SI  - GENBANK/AF065216
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Isoenzymes)
RN  - 0 (RNA, Messenger)
RN  - EC 3.1.1.32 (Phospholipases A)
RN  - EC 3.1.1.4 (Phospholipases A2)
SB  - IM
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Binding Sites/genetics
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 15/genetics
MH  - Cloning, Molecular
MH  - Exons/genetics
MH  - Gene Expression Regulation, Enzymologic/genetics
MH  - Humans
MH  - Introns/genetics
MH  - Isoenzymes/chemistry/genetics
MH  - Molecular Sequence Data
MH  - Phospholipases A/chemistry/*genetics
MH  - Phospholipases A2
MH  - RNA Splicing/genetics
MH  - RNA, Messenger/metabolism
MH  - Sequence Alignment
MH  - Sequence Analysis, DNA
MH  - Substrate Specificity
EDAT- 1999/03/20 00:00
MHDA- 1999/03/20 00:01
CRDT- 1999/03/20 00:00
PHST- 1999/03/20 00:00 [pubmed]
PHST- 1999/03/20 00:01 [medline]
PHST- 1999/03/20 00:00 [entrez]
AID - 10.1074/jbc.274.13.8823 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Mar 26;274(13):8823-31. doi: 10.1074/jbc.274.13.8823.