A growth factor-responsive gene of murine BALB/c 3T3 cells encodes a protein homologous to human tissue factor.

Hartzell, Stephen W.; Ryder, Kevin; Lanahan, Anthony A.; Lau, Lester F.; Nathan, David G.

doi:10.1128/mcb.9.6.2567

Cited by 124 publications

(92 citation statements)

References 38 publications

(36 reference statements)

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“…15 In recent years, however, it became evident that TF has additional biological functions apart from activating coagulation. One of the first indications for a nonhemostatic function of TF was its characterization as an immediate early gene that can be induced during cell division 16 and in response to pathophysiologically relevant stimuli, such as cytokines, 17 growth factors, 18 oxidized LDL, 19 and oxygen free radicals. 20 An exciting recent development in TF biology was the demonstration that this protein, a member of the cytokine receptor superfamily, can function as a true signaling receptor.…”

Section: Discussionmentioning

confidence: 99%

Tissue Factor Binding of Activated Factor VII Triggers Smooth Muscle Cell Proliferation via Extracellular Signal–Regulated Kinase Activation

et al. 2004

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Background-Tissue factor (TF) is the main initiator of coagulation in vivo. Recently, however, a role for TF as a cell receptor involved in signal transduction has been suggested. The aim of the present study was to assess whether activated factor VII (FVIIa) binding to TF could induce smooth muscle cell (SMC) proliferation and to clarify the possible intracellular mechanism(s) responsible for this proliferation. Methods and Results-Cell proliferation was induced by FVIIa in a dose-dependent manner, as assessed by [3 H]thymidine incorporation and direct cell counting, whereas no response was observed with active site-inhibited FVIIa (FVIIai), which is identical to FVIIa but is devoid of enzymatic activity. Similarly, no proliferation was observed when binding of FVIIa to TF was prevented by the monoclonal anti-TF antibody AP-1. Activation of the p44/42 mitogen-activated protein (MAP) kinase (extracellular signal-regulated kinases 1 and 2 [ERK 1/2]) pathway on binding of FVIIa to TF was demonstrated by transient ERK phosphorylation in Western blots and by suppression of proliferation with the specific MEK (MAP kinase/ERK kinase) inhibitor UO126. ERK phosphorylation was not observed with FVIIai or when cells were pretreated with AP-1. Conclusions-These data indicate a specific effect by which binding of FVIIa to TF on the surface of SMCs induces proliferation via a coagulation-independent mechanism and possibly indicate a new link between coagulation, inflammation, and atherosclerosis. Key Words: coagulants Ⅲ signal transduction Ⅲ cell division T issue factor (TF) is a cell surface-anchored glycoprotein that binds both the zymogen factor VII (FVII) and the active serine protease factor VIIa (FVIIa). 1 TF/FVIIa complex activates coagulation by cleaving its natural substrates, factors IX and X, ultimately leading to thrombin generation, fibrin deposition, and platelet activation. 1,2 On these grounds, TF has been considered to function as a major initiator of blood coagulation in vivo. Recently, however, some evidence has suggested that TF may mediate important coagulationindependent biological phenomena, including embryonic and oncogenic angiogenesis, 3,4 and inflammation. 5 In addition, recent data indicate that TF/FVIIa interaction may activate different intracellular signals, culminating in a variety of cell responses, thus suggesting a role for TF as a "true" cell membrane receptor. For example, TF/FVIIa interaction has been shown to be a strong chemotactic stimulus for smooth muscle cells (SMCs), mediating their migration in vitro. 6 FVIIa has been also shown to induce phosphorylation of the extracellular signalregulated kinases 1 and 2 (ERK 1/2) 7 and to upregulate poly(A) polymerase, 8 urokinase-type plasminogen activator receptor, 9 and a host of genes identified with the use of cDNA microarrays. 10 However, despite evidence suggesting close links between TF, activation of coagulation, and intracellular signaling, no direct effects of TF/FVIIa on SMC proliferation have yet been demonstrated. Thus, in the pr...

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Section: Discussionmentioning

confidence: 99%

Tissue Factor Binding of Activated Factor VII Triggers Smooth Muscle Cell Proliferation via Extracellular Signal–Regulated Kinase Activation

et al. 2004

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“…The pXT1 expression vector (Stratagene, Heidelberg, Germany) was used for constructing the tissue factor expression system (17)(18)(19)(20). Murine tissue factor cDNA was generously provided by Dr. Nathans (21). The full-length tissue factor cDNA was inserted into pXT1 from 3 Ј to 5 Ј for the tissue factor antisense construct (pXTF-as) or from 5 Ј to 3 Ј for the tissue factor sense construct (pXTF-s) (17).…”

Section: Methodsmentioning

confidence: 99%

Intravenous somatic gene transfer with antisense tissue factor restores blood flow by reducing tumor necrosis factor-induced tissue factor expression and fibrin deposition in mouse meth-A sarcoma.

Zhang

Deng²,

Wendt³

et al. 1996

J. Clin. Invest.

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“…Chemical stimuli such as phorbol ester 12-O -tetradecanoyl-13-phorbol-acetate (TPA), tumor necrosis factor-␣ (TNF-␣ ), bacterial endotoxin LPS, and IL-1 ␤ induce the expression of TF mRNA in cultured ECs (8)(9)(10)(11). TF was also induced in fibroblasts and COS-7 cells by serum and growth factors, including platelet-derived growth factor (PDGF), basic-fibroblast growth factor (b-FGF), and transforming growth factor-␤ (TGF-␤ ) (12)(13)(14). In the 5 Ј promoter region of the TF gene, there are several cis -elements, including TPA-responsive elements (TRE), B, Sp1, and EGR-1 (14).…”

Section: Introductionmentioning

confidence: 99%

Shear stress induction of the tissue factor gene.

et al. 1997

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Using flow channel, we report that the application of a laminar shear stress induced a transient increase of tissue factor (TF) procoagulant activity in human umbilical vein endothelial cells (HUVEC), which was accompanied by a rapid and transient induction of the TF mRNA in the HUVEC. Functional analysis of the 2.2 kb TF 5 Ј promoter indicated that a GC-rich region containing three copies each of the EGR-1 and Sp1 sites was required for induction. Mutation of the Sp1 sites, but not the EGR-1 sites, attenuated the response of TF promoter to shear stress. Thus, Sp1 is a newly defined shear stress responsive element. Electrophoretic mobility shift assays showed there was no increase in binding of nuclear extracts from sheared cells to an Sp1 consensus site. In contrast, immunoblotting of these nuclear extracts with antibody against transcription factor Sp1 demonstrated that shear stress increased the phosphorylation of Sp1. We also showed that shear stress, like the phosphatase inhibitor okadaic acid, increased the transcriptional activity of Sp1. These findings suggest that the shear stress induction of TF gene expression is mediated through an increased Sp1 transcriptional activity with a concomitant hyperphosphorylation of Sp1. ( J. Clin. Invest. 1997. 99:737-744.)

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A growth factor-responsive gene of murine BALB/c 3T3 cells encodes a protein homologous to human tissue factor.

Cited by 124 publications

References 38 publications

Tissue Factor Binding of Activated Factor VII Triggers Smooth Muscle Cell Proliferation via Extracellular Signal–Regulated Kinase Activation

Tissue Factor Binding of Activated Factor VII Triggers Smooth Muscle Cell Proliferation via Extracellular Signal–Regulated Kinase Activation

Intravenous somatic gene transfer with antisense tissue factor restores blood flow by reducing tumor necrosis factor-induced tissue factor expression and fibrin deposition in mouse meth-A sarcoma.

Shear stress induction of the tissue factor gene.

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