N‐linked glycosylation of platelet P2Y12 ADP receptor is essential for signal transduction but not for ligand binding or cell surface expression

FEBS Letters

Kumar, Ravindra¹  Kriz, Ron¹  Seehra, Jasbir¹  Zhong, Xiaotian¹ 

[1] Department of Chemical and Screening Sciences, Wyeth Research, 85 Bolton Street, Cambridge, MA 02140, USA

关键词: Adenosine diphosphate receptor;    N-linked glycosylation;    G protein-coupled receptor;    Adenylyl cyclase;    Surface expression;    Signal transduction;    2MeSADP;    2-methyl-thiol-adenosine diphosphate;    2MeSAMP;    2-methyl-thiol-adenosine monophosphate;    IBMX;    3-isobutyl-1-methylxanthine;    PCR;    polymerase chain reaction;    HA;    hemagglutinin;    DMEM;    Dulbecco's modified Eagle's medium;    FACS;    fluorescence-activated cell sorter;   

DOI  :  10.1016/S0014-5793(04)00191-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

P₂Y₁₂ 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 P₂Y₁₂ receptor is defective in the P₂Y₁₂-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.

【 授权许可】

Unknown