Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/11174
Title: Ferric ions inhibit proteolytic processing of progastrin.
Authors: Bramante, Gianni;Patel, Oneel;Shulkes, Arthur;Baldwin, Graham S
Affiliation: The University of Melbourne, Department of Surgery, Austin Health, Heidelberg, 3084 Victoria, Australia
Issue Date: 30-Dec-2010
Citation: Biochemical and Biophysical Research Communications 2010; 404(4): 1083-7
Abstract: The gastrointestinal hormone gastrin is generated from an 80 amino acid precursor (progastrin) by cleavage after dibasic residues by prohormone convertase 1. Phosphorylation of Ser(75) has previously been suggested, on the basis of indirect evidence, to inhibit cleavage of progastrin after Arg(73)Arg(74). Gastrins bind two ferric ions with high affinity, and iron binding is essential for the biological activity of non-amidated gastrins in vitro and in vivo. This study directly investigated the effect of iron binding and of serine phosphorylation on the cleavage of synthetic progastrin-derived peptides. The affinity of synthetic progastrin(55-80) for ferric ions, and the rate of cleavage by prohormone convertase 1, were not affected by phosphorylation of Ser(75). In contrast, in the presence of ferric ions the rate of cleavage of both progastrin(55-80) and phosphoSer(75)progastrin(55-80) by prohormone convertase 1 was significantly reduced. Hence iron binding to progastrin may regulate processing and secretion in vivo, and regulation may be particularly important in diseases with altered iron homeostasis.
Internal ID Number: 21195058
URI: http://ahro.austin.org.au/austinjspui/handle/1/11174
DOI: 10.1016/j.bbrc.2010.12.117
URL: http://www.ncbi.nlm.nih.gov/pubmed/21195058
Type: Journal Article
Subjects: Amino Acid Sequence
Gastrins.chemistry.metabolism
Humans
Iron.chemistry.metabolism
Molecular Sequence Data
Phosphorylation
Phosphoserine.metabolism
Proprotein Convertase 1.metabolism
Protein Precursors.chemistry.metabolism
Serine.metabolism
Trypsin.metabolism
Appears in Collections:Journal articles

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