A novel calcium-independent phospholipase A2, cPLA2-γ, that is prenylated and contains homology to cPLA2

Abstract

We report the cloning and characterization of a novel membrane-bound, calcium-independent PLA2, named cPLA2-γ. The sequence encodes a 541-amino acid protein containing a domain with significant homology to the catalytic domain of the 85-kDa cPLA2 (cPLA2-α). cPLA2-γ does not contain the regulatory calcium-dependent lipid binding (CaLB) domain found in cPLA2- α. However, cPLA2-γ 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-γ. Interestingly, cPLA2-γ demonstrates a preference for arachidonic acid at the sn-2 position of phosphatidylcholine as compared with palmitic acid. cPLA2-γ encodes a 3-kilobase message, which is highly expressed in heart and skeletal muscle, suggesting a specific role in these tissues. Identification of cPLA2-γ reveals a newly defined family of phospholipases A2 with homology to cPLA2-α.