N-linked glycosylation of platelet P2Y12 ADP receptor is essential for signal transduction but not for ligand binding or cell surface expression.
P(2)Y(12) receptor is a G(i)-coupled adenosine diphosphate (ADP) receptor with a critical role in platelet aggregation. It contains two potential N-linked glycosylation sites at its extra cellular amino-terminus, which may modulate its activity. Studies of both tunicamycin treatment and site-directed mutagenesis have revealed a dispensable role of the N-linked glycosylation in the receptor's surface expression and ligand binding activity. However, the non-glycosylated P(2)Y(12) receptor is defective in the P(2)Y(12)-mediated inhibition of the adenylyl cyclase activity. Thus the study uncovers an unexpected vital role of N-linked glycans in receptor's signal transducing step but not in surface expression or ligand binding.
Zhong
Xiaotian
X
Department of Chemical and Screening Sciences, Wyeth Research, 85 Bolton Street, Cambridge, MA 02140, USA.
Kriz
Ron
R
Seehra
Jasbir
J
Kumar
Ravindra
R
D000244:Adenosine Diphosphate / Q000378:metabolism; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D006031:Glycosylation; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism*; D058925:Receptors, Purinergic P2Y12; D015398:Signal Transduction / Q000502:physiology*
D000067956:Adenylyl Cyclase Inhibitors; D008024:Ligands; D008565:Membrane Proteins; D011134:Polysaccharides; D018048:Receptors, Purinergic P2; D058925:Receptors, Purinergic P2Y12; D000244:Adenosine Diphosphate; D000262:Adenylyl Cyclases