This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 25/12/2679    most recent 01.ATV.0000189305.84297.8bv1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Smolarczyk, K. Articles by Cierniewski, C. S. Search for Related Content PubMed PubMed Citation Articles by Smolarczyk, K. Articles by Cierniewski, C. S. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:2679.)
© 2005 American Heart Association, Inc.

Thrombosis

Fibrinogen Contains Cryptic PAI-1 Binding Sites That Are Exposed on Binding to Solid Surfaces or Limited Proteolysis

Katarzyna Smolarczyk; Joanna Boncela; Jacek Szymanski; Ann Gils; Czeslaw S. Cierniewski

From the Center of Medical Biology (K.S., J.B., C.S.C.), Polish Academy of Sciences, Lodz; the Department of Molecular and Medical Biophysics (J.S., C.S.C.), Medical University in Lodz, Poland; and the Laboratory for Pharmaceutical Biology and Phytopharmacology (A.G.), Katholieke Universiteit Leuven, Belgium.

Correspondence to Czeslaw S. Cierniewski, PhD, Department of Medical and Molecular Biophysics, Medical University in Lodz, 92-213 Lodz, 6/8 Mazowiecka St. E-mail cciern{at}zdn.am.lodz.pl

Objective— In this work, we identified the fibrinogen sequence that on exposure serves as the primary binding site for functionally active PAI-1 and to a lesser extent for its latent form. In contrast, this site only weakly interacts with PAI-1 substrate.

Methods and Results— The binding site is located in the N-terminal (20-88) segment of fibrinogen, in the region exposed on (1) adsorption of fibrinogen to solid surfaces; (2) the release of fibrinopeptide A during thrombin conversion of fibrinogen to fibrin; and (3) plasmin degradation of fibrinogen. This region was first identified by the yeast 2-hybrid system, then its binding characteristics were evaluated using the recombinant (16-120) fragment and its shorter version, the (20-88) fragment, in a solid phase binding assay and plasmon surface resonance measurements. Because fibrinogen fragment E does not bind PAI-1, it suggests that sequences of A chain interacting with PAI-1 are located in the N-terminal part of the (20-88) segment.

Conclusions— Therefore, PAI-1 directly bound to the (20-88) and thus concentrated in fibrinogen/fibrin, particularly at sites of injury and inflammation, may account for the recent observations that both its active and latent forms stimulate cell migration and wound healing.

We showed that PAI-1 is directly bound to the (20-88) and thus its concentration on fibrinogen/fibrin, particularly at sites of injury and inflammation, may account for the recent observations that both its active and latent forms stimulate cell migration and wound healing.

Key Words: conformational changes • fibrinogen • PAI-1 binding sites • proteolysis

This article has been cited by other articles:

				Y.-H. Guo, I. Hernandez, B. Isermann, T.-b. Kang, L. Medved, R. Sood, E. J. Kerschen, T. Holyst, M. W. Mosesson, and H. Weiler Caveolin-1-dependent apoptosis induced by fibrin degradation products Blood, April 30, 2009; 113(18): 4431 - 4439. [Abstract] [Full Text] [PDF]