On the Diversity of Secreted Phospholipases A2

Abstract

Over the last decade, an expanding diversity of secreted phospholipases A2 (sPLA2s) has been identified in mammals. Here, we report the cloning in mice of threeadditional sPLA2s called mouse group IIE (mGIIE), IIF (mGIIF), and X (mGX) sPLA2s, thus giving rise to eight distinct sPLA2s in this species. Both mGIIE and mGIIF sPLA2s contain the typical cysteines of group II sPLA2s, but have relatively low levels of identity (less than 51%) with other mouse sPLA2s, indicating that these enzymes are novel group II sPLA2s. However, a unique feature of mGIIF sPLA2 is the presence of a C-terminal extension of 23 amino acids containing a single cysteine. mGX sPLA2 has 72% identity with the previously cloned human group X (hGX) sPLA2 and displays similar structural features, making it likely that mGX sPLA2 is the ortholog of hGX sPLA2. Genes for mGIIE and mGIIF sPLA2s are located on chromosome 4, and that of mGX sPLA2 on chromosome 16. Northern and dot blot experiments with 22 tissues indicate that all eight mouse sPLA2s have different tissue distributions, suggesting specific functions for each. mGIIE sPLA2 is highly expressed in uterus, and at lower levels in various other tissues. mGIIF sPLA2 is strongly expressed during embryogenesisand in adult testis. mGX sPLA2 is mostly expressed in adult testis and stomach. When the cDNAs for the eight mouse sPLA2s were transiently transfectedin COS cells, sPLA2 activity was found to accumulate in cell medium, indicating that each enzyme is secreted and catalytically active. Using COS cell medium as asource of enzymes, pH rate profile and phospholipid headgroup specificity of the novel sPLA2s were analyzed and compared with the other mouse sPLA2s.