Plasmin degradation of insulin-like growth factor binding protein-5
(igfbp-5): regulation by igfbp-5201-218.
Campbell, Phil G., and Dennis L. Andress.
Orthopaedic Research Laboratory, Allegheny University of the Health
Sciences, Pittsburgh, PA 15212, and the Departments of Medicine,
Veteran Affairs Medical Center and University of Washington, Seattle,
WA 98108
APStracts 4:0163E, 1997.
Using the major bone insulin-like growth factor binding protein
(IGFBP), IGFBP-5, we took a mechanistic approach in evaluating the
role of the heparin-binding domain of IGFBP-5 in regulating plasmin
(Pm) proteolysis of IGFBP-5. Using synthetic IGFBP-5 peptide
fragments, we determined that the HE-binding domain, IGFBP-5201-218,
inhibits Pm proteolysis of intact IGFBP-5. The mechanism of action of
IGFBP-5201-218 was by inhibiting Pm binding to substrate IGFBP-5.
IGFBP-5201-218 action was independent of site of proteolysis, fluid
or solid phase interaction. In addition, IGFBP-5201-218 was found to
inhibit plasminogen (Pg) activation to Pm. IGFBP-5201-218 did not
directly inhibit the activity of Pm, urokinase Pg activator (uPA), or
tissue-type PA (tPA), but acted as a competitive inhibitor of Pg
activation by PA, which is in contrast to the stimulating effect of
heparin on Pg activation. These data indicate that the heparin
-binding domain contains the serine protease (Pg/Pm) binding site
region of IGFBP-5, and that this region which is presumed to
represent a Pm-induced proteolytic product of IGFBP-5, is capable of
regulating plasmin action.
Received 28 March 1997; accepted in final form 22 July 1997.
APS Manuscript Number E145-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 27 August 1997