AJP - Endo Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Endocrinol Metab 275: E321-E331, 1998;
0193-1849/98 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Campbell, P. G.
Right arrow Articles by Powell, D. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Campbell, P. G.
Right arrow Articles by Powell, D. R.
Vol. 275, Issue 2, E321-E331, August 1998

Plasminogen binds the heparin-binding domain of insulin-like growth factor-binding protein-3

Phil G. Campbell1, Susan K. Durham2, Adisak Suwanichkul2, James D. Hayes1, and David R. Powell2

1 Orthopaedic Research Laboratory, Allegheny University of Health Sciences, Pittsburgh, Pennsylvania 15212; and 2 Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030

Limited proteolysis lowers affinity of insulin-like growth factor (IGF)-binding protein (IGFBP)-3 for bound IGFs, resulting in greater IGF bioavailability. Plasmin is one of many proteases that cleave IGFBP-3, and the plasmin system may regulate IGFBP-3 proteolysis and IGF bioavailability in cultured cells in vitro. A role for the plasmin system in IGFBP-3 proteolysis in vivo is suggested by data presented here showing that IGFBP-3 binds plasminogen (Pg; Glu-Pg) with a dissociation constant (Kd) ranging from 1.43 to 3.12 nM. IGF-I and Glu-Pg do not compete for IGFBP-3 binding; instead, the binary IGFBP-3/Glu-Pg complex binds IGF-I with high affinity (Kd = 0.47 nM) to form a ternary complex. Competitive binding studies suggest that the kringle 1, 4, and 5 domains of Glu-Pg and the heparin-binding domain of IGFBP-3 participate in forming the IGFBP-3/Glu-Pg complex, and other studies show that Glu-Pg in this complex is activated at a normal rate by tissue Pg activator. Importantly, IGFBP-3/Glu-Pg complexes were detected in both human citrate plasma and serum, indicating that these complexes exist in vivo. Binding of IGFBP-3 to Glu-Pg in vivo suggests how Glu-Pg activation can specifically lead to IGFBP-3 proteolysis with subsequent release of IGFs to local target tissues.

plasmin; insulin-like growth factors; proteolysis; kringle domains; tissue plasminogen activator


This article has been cited by other articles:


Home page
 Cancer Res.Home page
H.-Y. Lee, K.-H. Chun, B. Liu, S. A. Wiehle, R. J. Cristiano, W. K. Hong, P. Cohen, and J. M. Kurie
Insulin-like Growth Factor Binding Protein-3 Inhibits the Growth of Non-Small Cell Lung Cancer
Cancer Res., June 1, 2002; 62(12): 3530 - 3537.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Fanayan, S. M. Firth, and R. C. Baxter
Signaling through the Smad Pathway by Insulin-like Growth Factor-binding Protein-3 in Breast Cancer Cells. RELATIONSHIP TO TRANSFORMING GROWTH FACTOR-beta 1 SIGNALING
J. Biol. Chem., February 22, 2002; 277(9): 7255 - 7261.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
B. A. Booth, M. Boes, B. L. Dake, K. L. Knudtson, and R. S. Bar
IGFBP-3 binding to endothelial cells inhibits plasmin and thrombin proteolysis
Am J Physiol Endocrinol Metab, January 1, 2002; 282(1): E52 - E58.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
R. C. Baxter
Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities
Am J Physiol Endocrinol Metab, June 1, 2000; 278(6): E967 - E976.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. G. Campbell, S. K. Durham, J. D. Hayes, A. Suwanichkul, and D. R. Powell
Insulin-like Growth Factor-binding Protein-3 Binds Fibrinogen and Fibrin
J. Biol. Chem., October 15, 1999; 274(42): 30215 - 30221.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online