Prosomatostatin is proteolytically processed at the amino terminal segment by subtilase SKI-1

DOIResolve DOI: http://doi.org/10.1016/j.regpep.2004.02.022
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TypeArticle
Volume120
Issue1-3
Pages133140; # of pages: 8
SubjectAcids; Amino Acids; Mutagenesis; Mutation; pha
AbstractProcessing of prohormones to generate active products typically occurs at basic residues via cleavage by proprotein convertases. A less common type of cleavage is mediated at hydrophobic (L, V, F, N) or small amino acid (A, T, S) residues. Efforts to identify the proteinases responsible for processing precursors at their hydrophobic amino acids has led to the recent cloning of a new type-1 membrane-bound subtilase called SKI-1. The NH(2)-terminal region of prosomatostatin, previously shown to contain a sorting signal for the regulated secretory pathways, is processed to generate PSST([1-10]). The exact cleavage mechanism is unknown, but has been assumed to involve monobasic processing at Lys(13) followed by carboxypeptidase trimming. We found that K13A mutation did not block PSST([1-10]) production. Since the prosomatostatin sequence R(8)-Q(9) -F(10)-L(11) downward arrow qualifies as a potential SKI-1 substrate, using a vaccinia virus expression system along with HPLC and radioimmunoassays, we observed that overexpression of recombinant SKI-1 in COS-1 and HEK-293 cells significantly increased the production of PSST([1-10]). Additionally, in CHO cells lacking SKI-1, there was a significant reduction in PSST([1-10]) production which could be increased upon SKI-1 stimulation. Mutagenesis studies showed that efficient processing of PSST to PSST([1-10]) required the RXRXXL motif. However, this NH(2)-terminal cleavage was not a prerequisite for the formation of SST-14 and SST-28
Publication date
AffiliationNRC Biotechnology Research Institute; National Research Council Canada
NoteEnglishNetherlands15177931
Peer reviewedNo
NRC number46211
NPARC number3540283
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Record identifiere521fcbc-7460-4240-86c0-f5e6ff1080f0
Record created2009-03-01
Record modified2016-05-09
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