HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor 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 Salemink, I. Articles by Lindhout, T. Search for Related Content PubMed PubMed Citation Articles by Salemink, I. Articles by Lindhout, T. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 40, 28225-28232, October 1, 1999

Inhibition of Tissue Factor-Factor VIIa-catalyzed Factor X Activation by Factor Xa-Tissue Factor Pathway Inhibitor
A ROTATING DISC STUDY ON THE EFFECT OF PHOSPHOLIPID MEMBRANE COMPOSITION

Irene Salemink, Jo Franssen, George M. Willems^§, H. Coenraad Hemker, and Theo Lindhout

From the  Department of Biochemistry and ^§ Cardiovascular Research Institute Maastricht, Maastricht University, 6200 MD Maastricht, The Netherlands

The physiological inhibitor of tissue factor (TF)·factor VIIa (FVIIa), full-length tissue factor pathway inhibitor (TFPI_FL) in complex with factor Xa (FXa), has a high affinity for anionic phospholipid membranes. The role of anionic phospholipids in the inhibition of TF·FVIIa-catalyzed FX activation was investigated. FXa generation at a rotating disc coated with TF embedded in a membrane composed of pure phosphatidylcholine (TF·PC) or 25% phosphatidylserine and 75% phosphatidylcholine (TF·PSPC) was measured in the presence of preformed complexes of FXa·TFPI_FL or FXa·TFPI_1-161 (TFPI lacking the third Kunitz domain and C terminus). At TF·PC, FXa·TFPI_FL and FXa·TFPI_1-161 showed similar rate constants of inhibition (0.07 × 10⁸ M¹ s¹ and 0.1 × 10⁸ M¹ s¹, respectively). With phosphatidylserine present, the rate constant of inhibition for FXa·TFPI_FL increased 3-fold compared with a 9-fold increase in the rate constant for FXa·TFPI_1-161. Incubation of TF·PSPC with FXa·TFPI_FL in the absence of FVIIa followed by depletion of solution FXa·TFPI_FL showed that FXa·TFPI_FL remained bound at the membrane and pursued its inhibitory activity. This was not observed with FXa·TFPI_1-161 or at TF·PC membranes. These data suggest that the membrane-bound pool of FXa·TFPI_FL may be of physiological importance in an on-site regulation of TF·FVIIa activity.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				T. M. Hackeng, K. M. Sere, G. Tans, and J. Rosing Protein S stimulates inhibition of the tissue factor pathway by tissue factor pathway inhibitor PNAS, February 28, 2006; 103(9): 3106 - 3111. [Abstract] [Full Text] [PDF]

				J. Ahamed, M. Belting, and W. Ruf Regulation of tissue factor-induced signaling by endogenous and recombinant tissue factor pathway inhibitor 1 Blood, March 15, 2005; 105(6): 2384 - 2391. [Abstract] [Full Text] [PDF]

				J. J. Briede, G. Tans, G. M. Willems, H. C. Hemker, and T. Lindhout Regulation of Platelet Factor Va-dependent Thrombin Generation by Activated Protein C at the Surface of Collagen-adherent Platelets J. Biol. Chem., March 2, 2001; 276(10): 7164 - 7168. [Abstract] [Full Text] [PDF]