Consensus Sequence for Precursor Processing at Mono-arginyl Sites : EVIDENCE FOR THE INVOLVEMENT OF A KEX2-LIKE ENDOPROTEASE IN PRECURSOR CLEAVAGES AT BOTH DIBASIC AND MONO-ARGINYL SITES

다국어 초록 (Multilingual Abstract)

Many peptide hormones and neuropeptides are produced from larger, inactive precursors though endoproteolysis at sites usually marked by paired basic residues (primarily Lys-Arg and Arg-Arg), or occasionally by a monobasic residue (primarily Arg). Based upon data concerning processing of prorenin and its mutants around the native Lys-Arg cleavage site expressed in mouse pituitary AtT-20 cells, we present the following sequence rules that govern mono-arginyl cleavages: (a) a basic residue at the fourth (position-4) or the sixth(position-6) residue upstream of the cleavage site is required, (b) at position - 4, Arg ; more favorable than Lys, and (c) at position I, a hydrophobic aliphatic residue is not suitable. These rules are compatible with those proposed by comparison of precursor sequences around mono-arginyl cleavage sites. We also provide evidence that precursor cleavages at mono-arginly and dibasic sites can be catalyzed by the same Kex2-like processing endoprotease, PC1/PC3.