A novel calcium-independent phospholipase A2, cPLA2-gamma, that is prenylated and contains homology to cPLA2.
We report the cloning and characterization of a novel membrane-bound, calcium-independent PLA2, named cPLA2-gamma. The sequence encodes a 541-amino acid protein containing a domain with significant homology to the catalytic domain of the 85-kDa cPLA2 (cPLA2-alpha). cPLA2-gamma does not contain the regulatory calcium-dependent lipid binding (CaLB) domain found in cPLA2-alpha. However, cPLA2-gamma does contain two consensus motifs for lipid modification, a prenylation motif (-CCLA) at the C terminus and a myristoylation site at the N terminus. We present evidence that the isoprenoid precursor [3H]mevalonolactone is incorporated into the prenylation motif of cPLA2-gamma. Interestingly, cPLA2-gamma demonstrates a preference for arachidonic acid at the sn-2 position of phosphatidylcholine as compared with palmitic acid. cPLA2-gamma encodes a 3-kilobase message, which is highly expressed in heart and skeletal muscle, suggesting a specific role in these tissues. Identification of cPLA2-gamma reveals a newly defined family of phospholipases A2 with homology to cPLA2-alpha.
Small Molecule Drug Discovery Group, Genetics Institute, Cambridge, Massachusetts 02140, USA.
K W
KW
Underwood
C
C
Song
R W
RW
Kriz
X J
XJ
Chang
J L
JL
Knopf
L L
LL
Lin
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006224:Cricetinae; D054513:Group IV Phospholipases A2; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010741:Phospholipases A / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification*; D054467:Phospholipases A2; D017368:Protein Prenylation; D016415:Sequence Alignment
D010741:Phospholipases A; D054513:Group IV Phospholipases A2; D054467:Phospholipases A2; D002118:Calcium