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 family. The native CD39 protein has two intracytoplasmic and two transmembrane domains. There is a large extracellular domain that undergoes extensive glycosylation and can be post-translationally modified by limited proteolysis. We have identified a potential thioester linkage site for S-acylation within the N-terminal region of CD39 and demonstrate that this region undergoes palmitoylation in a constitutive manner. The covalent lipid modification of this region of the protein appears to be important both in plasma membrane association and in targeting CD39 to caveolae. These specialized plasmalemmal domains are enriched in G protein-coupled receptors and appear to integrate cellular activation events. We suggest that palmitoylation could modulate the function of CD39 in regulating cellular signal transduction pathways.
Koziak
K
K
Department of Medicine, Center for Immunobiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Kaczmarek
E
E
Kittel
A
A
Sévigny
J
J
Blusztajn
J K
JK
Schulte Am Esch
J
J
Imai
M
M
Guckelberger
O
O
Goepfert
C
C
Qawi
I
I
Robson
S C
SC
D000251:Adenosine Triphosphatases; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001081:Apyrase / Q000378:metabolism*; D015153:Blotting, Western; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002855:Chromatography, Thin Layer; D003593:Cytoplasm / Q000378:metabolism; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000648:ultrastructure; D006801:Humans; D008854:Microscopy, Electron; D016296:Mutagenesis; D019308:Palmitic Acid / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
D015703:Antigens, CD; D019308:Palmitic Acid; D000251:Adenosine Triphosphatases; D001081:Apyrase; C067869:CD39 antigen