THE HUMAN 180-KDA RECEPTOR FOR SECRETORY PHOSPHOLIPASES A(2) - MOLECULAR-CLONING, IDENTIFICATION OF A SECRETED SOLUBLE FORM, EXPRESSION, AND LOCALIZATION

Secretory phospholipases A(2) (sPLA(2)) are structurally related enzym es found in mammals as well as in insect and snake venoms. They have b een associated with several physiological, pathological, and toxic pro cesses. Some of these effects are apparently linked to the existence o f specific receptors for both venom and mammalian sPLA(2)s. We report here the molecular cloning and expression of one of these sPLA(2) rece ptors from human kidney. Two transcripts were detected. One encodes fo r a transmembrane form of the sPLA(2) receptor and the other one is an alternatively processed transcript, caused by polyadenylation occurri ng at a site within an intron in the C terminus part of the transcript ional unit. This transcript encodes for a shortened secreted soluble s PLA(2) receptor lacking the coding region for the transmembrane segmen t, Quantitative polymerase chain reaction experiments indicate a 1.6:1 ratio between the levels of transcripts encoding for the membrane bou nd and soluble forms of the receptor, respectively. Soluble and membra ne bound human sPLA(2) receptors both bind sPLA(2) with high affinitie s. However, the binding properties of the human receptors are differen t from those obtained with the rabbit membrane-bound sPLA(2) receptor. The 180 kDa human sPLA(2) receptor gene has been mapped in the q23-q2 4 bands of chromosome 2.