Palmitoylation targets CD39/endothelial ATP diphosphohydrolase to caveolae

Ectonucleotidases influence purinergic receptor function by the hydrolysis of extracellular nucleotides, CD39 is an integral membrane protein that is a prototype member of the nucleoside 5'-triphosphate diphosphohydrolase fam ily. The native CD39 protein has two intracytoplasmic and two transmembrane domains. There is a large extracellular domain that undergoes extensive gl ycosylation and can be post-translationally modified by limited proteolysis , We have identified a potential thioester linkage site for S-acylation wit hin the N-terminal region of CD39 and demonstrate that this region undergoe s palmitoylation in a constitutive manner. The covalent lipid modification of this region of the protein appears to be important both in plasma membra ne association and in targeting CD39 to caveolae. These specialized plasmal emmal domains are enriched in G protein-coupled receptors and appear to int egrate cellular activation events. We suggest that palmitoylation could mod ulate the function of CD39 in regulating cellular signal transduction pathw ays.