title: Clarification of the C-terminal proteolytic processing site of human Amphiregulin.
abstract: Amphiregulin, like other ErbB ligands, is synthesized as a pro-protein which requires cleavage at the cell surface to release the active signaling domain. Prior studies using a variety of approaches have not yielded a consensus about the precise cleavage site. Here we report the purification and protein sequencing of the cell-associated human Amphiregulin stalk which remains following cleavage of the signaling domain. These data indicate that human Amphiregulin is cleaved at Lysine 187, a site homologous to the cleavage site reported in the mouse protein and distinct from the Lysine 184 site previously reported for the human protein.
authors.affiliation: Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Levano
authors.forename: Paraic A
authors.initials: PA
authors.lastname: Kenny
mesh_terms: D000595:Amino Acid Sequence; D066258:Amphiregulin; D000818:Animals; D001665:Binding Sites; D066255:EGF Family of Proteins; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; C587849:Areg protein, mouse; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D008239:Lysine