Tissue Factor Pathway Inhibitor Binds to Platelet Thrombospondin-1

Mast, Alan E.; Stadanlick, Jason; Lockett, Jaron; Dietzen, Dennis J.; Hasty, Karen A.; Hall, Connie L.

doi:10.1074/jbc.m006595200

Cited by 38 publications

(44 citation statements)

References 53 publications

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“…Furthermore, this TSR sequence has been found to bind MMPs (42), and interestingly, the full glycoprotein TSP1 was found to interact with the inhibitor TFPI, which is highly similar to TFPI-2. These authors, however, did not provide a detailed characterization of the domains implicated in the interaction (43).…”

Section: Discussionmentioning

confidence: 99%

ADAMTS1 Interacts with, Cleaves, and Modifies the Extracellular Location of the Matrix Inhibitor Tissue Factor Pathway Inhibitor-2

Torres-Collado

Kisiel

Iruela‐Arispe

et al. 2006

Journal of Biological Chemistry

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ADAMTS1 is an extracellular metalloproteinase known to participate in a variety of biological processes that includes inflammation, angiogenesis, and development of the urogenital system. Many of its functions rely on its catalytic activity, which thus far has been limited to the cleavage of the matrix proteoglycans aggrecan and versican. However, it is likely that other substrates exist. Using a yeast two-hybrid screen, we identified the Kunitz-type inhibitor, tissue factor pathway inhibitor-2 (TFPI-2), as a binding partner of ADAMTS1. The interaction was confirmed by several biochemical and cell-based assays. In addition, our studies revealed alterations in the pattern of TFPI-2-secreted isoforms and in its extracellular location caused by the specific action of ADAMTS1. Interestingly, we found that TFPI-2 is a novel substrate of ADAMTS1. The cleavage removes a protease-sensitive C-terminal region in TFPI-2, altering its binding properties. The proposed role of TFPI-2 as a maintenance factor of extracellular remodeling suggests the indirect function of ADAMTS1 as an additional homeostatic player by its ability to alter the extracellular location of TFPI-2 and, therefore, to disrupt the remodeling machinery, a phenomenon directly associated to pathologies such as atherosclerosis and tumor progression.The extracellular milieu has been recognized as a dynamic scenario that directly influences proliferation, survival, migration, and biosynthetic activities of cells. The constituents of this extracellular environment include growth factors, chemokines, cell surface proteins, and an extensive list of matrix components with structural and signaling properties. Matrix proteases and their respective inhibitors are also important components of the extracellular milieu with the added value that these molecules modify, degrade, or inflict functional alterations to most of the components previously listed (1). In fact, modification of extracellular components by processing and/or proteolysis is a frequent event during morphogenesis and tissue repair and, in an altered manner, during the progression of various pathological conditions (2).The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of proteases includes a group of 19 secreted enzymes with a more restricted spectrum of catalytic activities than the well known matrix metalloproteinases (MMP) 2 (3). ADAMTS1, the first member described (4), has been shown to display anti-angiogenic properties (5). Systemic deletion of adamts1 in mice resulted in multiple defects in the urogenital system (6, 7). The enzyme is known to have catalytic activity toward matrix proteoglycans, particularly versican and aggrecan (8,9).Mechanistically, it is not evident that the outcomes of the gene-deletion studies can be linked with the catalytic profile known for this enzyme. Thus, it is possible that either other domains contribute to the spectrum of biological functions and/or that additional biologically relevant substrates are yet to be identified. The modular...

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Section: Discussionmentioning

confidence: 99%

ADAMTS1 Interacts with, Cleaves, and Modifies the Extracellular Location of the Matrix Inhibitor Tissue Factor Pathway Inhibitor-2

Torres-Collado

Kisiel

Iruela‐Arispe

et al. 2006

Journal of Biological Chemistry

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“…Cleavage after K249 removes the C-terminal basic tail of TFPI, a region that facilitates TFPI binding to membranes 38 and membrane receptors. 39 Loss of this region would explain the segregation of proteolyzed TFPI to the supernatant fraction of TFPI pulldowns conducted with wild-type E coli ( Figure 5D). …”

Section: Discussionmentioning

confidence: 99%

Proteolytic inactivation of tissue factor pathway inhibitor by bacterial omptins

Yun¹,

Cott

Tapping

et al. 2009

Blood

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The immune response to infection includes activation of the blood clotting system, leading to extravascular fibrin deposition to limit the spread of invasive microorganisms. Some bacteria have evolved mechanisms to counteract this host response. Pla, a member of the omptin family of Gram-negative bacterial proteases, promotes the invasiveness of the plague bacterium, Yersinia pestis, by activating plasminogen to plasmin to digest fibrin. We now show that the endogenous anticoagulant tissue factor pathway inhibitor (TFPI) is also highly sensitive to proteolysis by Pla and its orthologs OmpT in Escherichia coli and PgtE in Salmonella enterica serovar Typhimurium. Using gene deletions, we demonstrate that bacterial inactivation of TFPI requires omptin expression. TFPI inactivation is mediated by proteolysis since Western blot analysis showed that TFPI cleavage correlated with loss of anticoagulant function in clotting assays. Rates of TFPI inactivation were much higher than rates of plasminogen activation, indicating that TFPI is a better substrate for omptins. We hypothesize that TFPI has evolved sensitivity to proteolytic inactivation by bacterial omptins to potentiate procoagulant responses to bacterial infection. This may contribute to the hemostatic imbalance in disseminated intravascular coagulation and other coagulopathies accompanying severe sepsis. (Blood. 2009;113: 1139-1148) IntroductionAside from its role in minimizing blood loss, the clotting system is also an effector arm of the immune system that modulates release of inflammatory mediators and prevents the spread of invasive microorganisms through extravascular fibrin deposition. This "quarantine through coagulation" strategy is evolutionarily primitive, as evidenced by the sensitivity of the horseshoe crab clotting system to activation by bacterial endotoxin. 1 Indeed, fibrin deposition is one of the hallmarks of inflammation in humans, and the induration accompanying delayed-type hypersensitivity skin reactions is caused by extravascular fibrin deposition. 2 Inflammatory responses to infection include expression of tissue factor on activated monocytes as well as increased acute phase proteins like fibrinogen and PAI-I, which contribute to hypercoagulable states. 3 Some bacteria modulate the host coagulation system to evade immune responses or facilitate dissemination through extravascular tissues. For example, staphylocoagulase and streptokinase form complexes with prothrombin or plasminogen, converting them into prothrombotic (thrombin) or profibrinolytic (plasmin) enzymes. 4 Likewise, plasminogen activator (Pla), a member of the omptin family of bacterial proteases, promotes dissemination of the plague agent, Yersinia pestis, from subcutaneous sites to the lymphatic and circulatory systems. 5 Proteolytic activation of plasminogen by Pla is thought to facilitate Y pestis migration through tissue barriers, because plasmin degrades fibrin clots and extracellular matrix components, activates procollagenases, and inactivates collagenase inhibitors. [6...

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“…3). However, other functional protein alterations of plasma proteins, such as protein S and a2-antiplasmin, have been described while using the solvent/detergent method [43,44].…”

Section: Clinical Applications -Biomarker Identificationmentioning

confidence: 99%

Recent advances in blood‐related proteomics

et al. 2005

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Service régional vaudois de transfusion sanguine, Lausanne, SwitzerlandBlood is divided in two compartments, namely, plasma and cells. The latter contain red blood cells, leukocytes, and platelets. From a descriptive medical discipline, hematology has evolved towards a pioneering discipline where molecular biology has permitted the development of prognostic and diagnostic indicators for disease. The recent advance in MS and protein separation now allows similar progress in the analysis of proteins. Proteomics offers great promise for the study of proteins in plasma/serum, indeed a number of proteomics databases for plasma/ serum have been established. This is a very complex body fluid containing lipids, carbohydrates, amino acids, vitamins, nucleic acids, hormones, and proteins. About 1500 different proteins have recently been identified, and a number of potential new markers of diseases have been characterized. Here, examples of the enormous promise of plasma/serum proteomic analysis for diagnostic/prognostic markers and information on disease mechanism are given. Within the blood are also a large number of different blood cell types that potentially hold similar information. Proteomics of red blood cells, until now, has not improved our knowledge of these cells, in contrast to the major progresses achieved while studying platelets and leukocytes. In the future, proteomics will change several aspects of hematology.

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Tissue Factor Pathway Inhibitor Binds to Platelet Thrombospondin-1

Cited by 38 publications

References 53 publications

ADAMTS1 Interacts with, Cleaves, and Modifies the Extracellular Location of the Matrix Inhibitor Tissue Factor Pathway Inhibitor-2

ADAMTS1 Interacts with, Cleaves, and Modifies the Extracellular Location of the Matrix Inhibitor Tissue Factor Pathway Inhibitor-2

Proteolytic inactivation of tissue factor pathway inhibitor by bacterial omptins

Recent advances in blood‐related proteomics

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