Proteolytic cleavage of the EMR2 receptor requires both the extracellular stalk and the GPS motif.
EMR2 is a human myeloid-restricted member of the EGF-TM7 receptor family that contains a highly conserved G protein-coupled receptor proteolysis site (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 alpha-subunit and transmembrane beta-subunit requires a minimum of eight amino acids in the beta-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.
Chang
Gin-Wen
GW
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, OX1 3RE, Oxford, UK.
Stacey
Martin
M
Kwakkenbos
Mark J
MJ
Hamann
Jörg
J
Gordon
Siamon
S
Lin
Hsi-Hsien
HH
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers; D010450:Endopeptidases / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005822:Genetic Vectors; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
C412456:ADGRE2 protein, human; D017931:DNA Primers; D010446:Peptide Fragments; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D010450:Endopeptidases