Igfbp-3 proteolysis by plasmin, thrombin, serum: heparin binding,
igf binding and structure of fragments.
Booth, Barbara A., Mary Boes, and Robert S. Bar.
Veterans Administation Medical Center, Department of Internal
Medicine, Diabetes and Endocrinology Research Center, The University
of Iowa, Iowa City, Iowa 52246
APStracts 3:0087E, 1996.
IGFBP-3 was exposed to plasmin, thrombin and pregnancy serum,
substances normally present at the endothelial surface in enriched
concentrations. The N-termini of the proteolytic fragments were
sequenced and their ability to bind IGF and heparin assessed by
ligand blotting. Plasmin generated at least 5 fragments, 3 beginning
at the N-terminus of IGFBP-3 and 2 with N-termini corresponding to
middle portions of IGFBP-3. The dominant fragment bound both IGF and
heparin while N-terminal fragments bound only IGF. Thrombin generated
3, and serum 5 easily identified fragments; the dominant fragments,
beginning at midportions of IGFBP-3, retained IGF and heparin
affinity whereas the remaining fragments had differential affinities
for IGF and heparin. We suggest that such fragments, when generated
at the endothelial surface, have the potential to alter regional
vascular concentrations of IGF and thus influence both IGF and
endothelial function.
Received 3 January 1996; accepted in final form 5 April 1996.
APS Manuscript Number E56-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96