STRUCTURAL COMPARISON OF PHOSPHOLIPASE-A(2)-BINDING REGIONS IN PHOSPHOLIPASE-A(2) RECEPTORS FROM VARIOUS MAMMALS

We determined the nucleotide sequence of a mouse cDNA encoding the receptor for pancreatic group I phospholipase A(2) (PLA(2)-I). Interspecies structural comparison of the mouse receptor with bovine PLA(2)-I receptor, whose structure had been clarified, revealed that the fourth carbohydrate-recognition domain (CRD)-like domain (CRD-like 4) was the most conserved among the domains in the PLA(2)-I receptor, suggesting the functional importance of CRD-like 4. A transient expression experiment with a truncated form of the receptor consisting of three CRD-like domains, from the third to the fifth, demonstrated that the PLA(2)-I-binding site of the receptor is constituted from these three CRD-like domains, supporting the functional indispensability of CRD-like 4 in the receptor. Since the PLA(2)-I-binding region was thus assigned to be CRD-like domains 3-5, we further analyzed the structures of the PLA(2)-I-binding regions in the PLA(2)-I receptors from the rat, rabbit and human. Furthermore, the obtained PLA(2)-I receptor cDNA fragments from these animals made it possible to examine the tissue expression patterns of this receptor in various mammals. The results, together with the results of the genomic structural analysis of this gene, indicated that a PLA, receptor recently characterized by Lambeau et al. [Lambeau, G., Ancian, P., Barhanin, J. and Lazdunski, M. (1994) J. Biol. Chem. 269, 1575-1578] is a rabbit counterpart of the PLA(2)-I receptor although these two PLA(2) receptors have distinctive PLA(2)-binding specificities.