Proteolytic cleavage of the EMR2 receptor requires both the extracellular stalk and the GPS motif

FEBS Letters

Stacey, Martin¹  Lin, Hsi-Hsien¹  Gordon, Siamon¹  Kwakkenbos, Mark J.²  Chang, Gin-Wen¹  Hamann, Jörg² 

[1]Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK

[2]Laboratory for Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

关键词: Post-translational modification;    Proteolytic cleavage;    ECD;    extracellular domain;    FACS;    fluorescence-activated cell sorting;    Fc;    fragment crystallisable;    GPCR;    G protein-coupled receptor;    GPS;    GPCR proteolysis site;    LNB-TM7;    long N-terminal family B GPCR-related 7TM receptor;    PAGE;    polyacrylamide gel electrophoresis;    TM;    transmembrane;   

DOI  :  10.1016/S0014-5793(03)00695-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

EMR2 is a human myeloid-restricted member of the EGF-TM7 receptor family that contains a highly conserved protein-coupled receptor roteolysis ite (GPS) in the membrane-proximal region. Here the post-translational proteolytic cleavage of EMR2 at GPS was investigated. We show the cleavage occurs at Leu⁵¹⁷-Ser⁵¹⁸ and is independent of the transmembrane domains. The non-covalent association of the resulting extracellular α-subunit and transmembrane β-subunit requires a minimum of eight amino acids in the β-subunit. The GPS motif is necessary, but not sufficient for receptor cleavage, which requires the entire extracellular stalk. Thus, an alternatively spliced EMR2 isoform with a truncated stalk fails to undergo proteolytic cleavage. Alternative splicing therefore provides a means to regulate GPS cleavage, producing receptors with two distinct structures.

【 授权许可】

Unknown