Pancreatic islets express a Ca²⁺-independent phospholipase A₂ enzyme that contains a repeated structural motif homologous to the integral membrane protein binding domain of ankyrin

Pancreatic islets express a Ca²⁺-independent phospholipase A₂ (CaI- PLA₂) activity that is sensitive to inhibition by a haloenol lactone suicide substrate that also attenuates glucose-induced hydrolysis of arachidonic acid from islet phospholipids and insulin secretion. A cDNA has been cloned from a rat islet cDNA library that encodes a protein with a deduced amino acid sequence of 751 residues that is homologous to a CaI-PLA₂ enzyme recently cloned from Chinese hamster ovary cells. Transient transfection of both COS- 7 cells and Chinese hamster ovary cells with the cloned islet CaI-PLA₂ cDNA resulted in an increase in cellular CaI-PLA₂ activity, and this activity was susceptible to inhibition by haloenol lactone suicide substrate. The domain of the islet CaI-PLA₂ from amino acid residues 150-414 is composed of eight stretches of a repeating sequence motif of approximately 33-amino acid residues in length that is highly homologous to domains of ankyrin that bind both tubulin and integral membrane proteins, including several proteins that regulate ionic fluxes across membranes. These findings complement previous pharmacologic observations that suggest that CaI-PLA₂ may participate in regulating transmembrane ion flux in glucose-stimulated β-cells.