A NOVEL CALCIUM-INDEPENDENT PHOSPHOLIPASE A(2), CPLA(2)-GAMMA, THAT IS PRENYLATED AND CONTAINS HOMOLOGY TO CPLA(2)

We report the cloning and characterization of a novel membrane-bound, calcium-independent PLA(2), named cPLA(2)-gamma. The sequence encodes a 541-amino acid protein containing a domain with significant homology to the catalytic domain of the 85-kDa cPLA(2) (cPLA(2)-alpha). cPLA(2 )-gamma does not contain the regulatory calcium-dependent lipid bindin g (CaLB) domain found in cPLA(2)-alpha. However, cPLA(2)-gamma does co ntain 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 [H-3]mevalonolacto ne is incorporated into the prenylation motif of cPLA(2)-gamma. Intere stingly, cPLA(2)-gamma demonstrates a preference for arachidonic acid at the sn-2 position of phosphatidylcholine as compared with palmitic acid. cPLA(2)-gamma encodes a 3-kilobase message, which is highly expr essed in heart and skeletal muscle, suggesting a specific role in thes e tissues. identification of cPLA(2)-gamma reveals a newly defined fam ily of phospholipases A(2) with homology to CPLA(2)-alpha.