© 1996 American Heart Association, Inc.
Articles |
Thrombin-Induced Increase in Endothelial Permeability Is Associated With Changes in Cell-to-Cell Junction Organization
From CEA, Laboratoire d'Hématologie, INSERM U217, Département de Biologie Moléculaire et Structurale, Grenoble, France, and Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy (M.-G.L.).
Correspondence to Dr M.-J. Rabiet, Laboratoire d'Hématologie, INSERM U 217, Département de Biologie Moléculaire et Structurale, CEN-G, 17 rue des Martyrs, 38054 Grenoble Cedex, France.
 |
Abstract |
|---|
 Top Abstract IntroductionMethods Results Discussion References |
|---|
Abstract Thrombin increases endothelial permeability in a rapid and reversible way. This effect requires the catalytic activity of the enzyme and thrombin receptor engagement. Endothelial cell permeability is mostly regulated by intercellular junction organization. In the present study, we investigated whether opening of intercellular gaps after thrombin treatment could be related to changes in adherence-junction molecular organization. By immunofluorescence analysis, we found that thrombin stimulation of endothelial cells caused a marked alteration of the distribution of vascular endothelial (VE)-cadherin and of the associated catenins. These molecules, which are strictly localized at intercellular boundaries in confluent resting cells, were absent in the areas of intercellular retraction. Immunoprecipitation analysis indicated that thrombin disrupted the VE-cadherin/catenin complex. This effect was reversible and correlated with the increase in endothelial permeability. The use of a protein kinase C inhibitor (calphostin C) blocked both thrombin-induced permeability and disassembly of adherence-junction components. We propose that thrombin's effect on endothelial cell junction organization is an important determinant in the increase in endothelial permeability induced by this agent.
Key Words: endothelial monolayer • thrombin • cadherin • catenins
|
Introduction |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Thrombin induces profound alterations of endothelial cell monolayer permeability in vitro and in vivo. Intravenous infusion of thrombin was found to be a potent stimulus for increased pulmonary vascular permeability to proteins that ultimately results in pulmonary edema.1 In addition, changes in endothelial cell permeability have been associated with early phases of atherosclerosis.2 The mechanism of thrombin-induced alteration of endothelial permeability remains to be fully characterized. Thrombin receptor cleavage and the consequent combined elevation of intracellular calcium and PKC activation seem to be required for thrombin to have an effect.3 4 These processes would sequentially lead to stimulation of an endothelial contractile reaction, with the eventual development of intercellular gaps. Actin filaments at the periphery of endothelial cells are linked to cell-to-cell adherence junctions. These organelles are formed by transmembrane calcium-dependent adhesive proteins called cadherins, which are associated inside the cells with a complex network of cytoskeletal molecules that in turn promote the anchorage to actin microfilaments.5 6 7 8 9 10 An endothelium-specific cadherin has been identified. This molecule was named VE-cadherin (cadherin-5,11 or 7B412 ). VE-cadherin, similarly to the other members of the family, is complexed with cytoplasmic proteins termed
-catenin,
ß-catenin, and plakoglobin (or 
-catenin), which in turn
promote its anchorage to the actin cytoskeleton.13 Such a
high order of structure must be dynamic and capable of responding to
cellular signals. In the present study, we investigated whether disruption of endothelial cell barrier function induced by thrombin is associated with changes in the organization of adherence junctions. Immunofluorescence studies showed that thrombin caused endothelial cell retraction accompanied by a redistribution of VE-cadherin and catenins in the areas of intercellular gap formation. Immunoprecipitation analysis indicated that thrombin activation of endothelial cells induced disruption of the VE-cadherin/catenin complex. This effect paralleled the effect of the enzyme on endothelial barrier properties. We suggest that alteration of adherence-junction organization is related to thrombin-induced increase in endothelial permeability.
|
Methods |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Cell Culture
HUVECs were isolated from normal-term umbilical cord veins by collagenase perfusion as previously described.14 Cells were grown on Falcon tissue culture flasks (Becton Dickinson) coated with 0.5% gelatin (Sigma Chemical Co) in 20% newborn calf serum/M199 medium (GIBCO-BRL) supplemented with 50 µg/mL endothelial cell growth supplement prepared from bovine brain and 100 µg/mL heparin (Sigma). Cells were used between the second and fourth passages.
The human endothelial cell line EA.hy92615 was obtained from C.J. Edgell (University of North Carolina, Chapel Hill, NC) and cultured in Dulbecco's modified Eagle's medium (GIBCO) supplemented with 10% fetal calf serum (GIBCO).
Reagents and Antibodies
Purified human - and
-thrombin were prepared as
described.16 A mammalian expression system was used to
obtain an active-site mutant thrombin (SA205 thrombin) devoid of
catalytic activity.17
TRAP14, corresponding to amino acids 42 through 55 (SFLLRNPNDKYEPF) of the human thrombin receptor,18 was synthesized on an Applied Biosystems peptide synthesizer and purified by high-performance liquid chromatography as described.17 PKC inhibitors (calphostin C and H7), staurosporine, and herbimycin A were purchased from Sigma.
Monoclonal antibodies to human VE-cadherin (clone
TEA1-31)13 and human plakoglobin (clone PG5-1, purchased
from IBL Research Products) were used. Rabbit polyclonal
antibodies against - and ß-catenin were kindly provided
by Dr D. Vestweber (Max Planck Institute for Immunology, Freibourg,
Germany) and D. Gulino (Laboratoire d'Hématologie, DBMS,
CEN-G, Grenoble, France). These antibodies were used at concentrations
previously indicated.13 Monoclonal antibody to p120 was
purchased from Transduction Laboratories and used at a 1/1000
dilution.
Transendothelial Permeability
Assay
The passage of HRP through confluent cell monolayers was
measured using Transwell cell culture chambers (Polycarbonate
filters, 0.4-µm pore size, Costar). HUVECs were seeded and grown as
previously described.12 EA.hy926 cells were seeded at
2x104 cells per filter in 200 µL Dulbecco's
modified
Eagle's medium with 10% fetal calf serum in the upper compartment.
The same medium (800 µL) filled the lower compartment. EA.hy926 cells
were grown for 3 days to attain confluence. At the start of the
experiment, the medium in the upper compartment was removed and
replaced by 200 µL of thrombin or TRAP14 at indicated concentrations
in serum-free medium. The lower compartment was refilled with 800
µL serum-free medium. After a 15-minute agonist treatment, the
medium in the upper compartment was removed and replaced by 200 µL
serum-free medium containing 0.5 µmol/L HRP. The lower
compartment was refilled with 800 µL serum-free medium. At
several time points, 20-µL samples were withdrawn from the lower
compartment. HRP concentration was determined spectrophotometrically by
assaying peroxidase activity on 5 mmol/L guaiacol in 50 mmol/L
Na2H2PO4 in the presence of 0.6
mmol/L hydrogen peroxide and measuring the increase in the absorbance
at 470 nm.19 20 HRP clearance rate was expressed in
micrograms per minute. In preliminary experiments, 15-minute incubation
was selected because, with all the thrombin concentrations used, it
resulted in maximal HRP passage.
Localization of Actin Filaments and
Immunofluorescence Staining
Confluent monolayers of HUVECs, grown on
fibronectin (7
µg/mL)-coated glass coverslips as described,12 and of
EA.hy926 cells, grown on Lab-Tek chamber slides (Poly Labo), were
treated with 10 nmol/L thrombin in serum-free medium for various
lengths of time. After thrombin treatment, cells were fixed and
permeabilized as described12 13 and
processed for immunofluorescence microscopy as
described earlier.21 Observations were performed with a
Zeiss microscope equipped for epifluorescence, and
fluorescence images were recorded on Kodak 400 films.
Immunoprecipitation and Western Blotting
Cell extraction and
immunoprecipitation with monoclonal
anti–VE-cadherin antibody TEA1-31 were performed on 500 µL of total
extract as previously described.13 Total extracts were
precleared with a 30-minute incubation at 4°C with 50 µL of protein
G Sepharose (Pharmacia). Na3VO4 (1 mmol/L) was
added to all buffers used.
After SDS–polyacrylamide gel electrophoresis on a 7.5% polyacrylamide gel, the separated proteins were electrotransferred for 5 hours at 70 V onto Hybond ECL nitrocellulose (Amersham) in 50 mmol/L Tris-HCl, 95 mmol/L glycine, and 1 mmol/L CaCl2. The membrane was blocked with 10% low-fat milk in calcium-magnesium Dulbecco's PBS (purchased from Sigma) and incubated overnight with primary antibodies diluted in 10% low-fat milk in PBS. After washing in PBS containing 0.05% Tween 20, the membrane was incubated for 1 hour at room temperature with HRP-conjugated secondary antibodies of the appropriate species, developed with enhanced chemiluminescence reagent (Amersham), and exposed to hyperfilm ECL (Amersham).
|
Results |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Characterization of Thrombin-Induced Permeability of HUVEC and EA.hy926 Cell Monolayers
In agreement with published work,22 in preliminary experiments, we observed some variability in the response to thrombin of HUVECs obtained from different umbilical cords. We therefore assayed whether we could standardize the system using an immortalized cell line. Among a series of endothelial lines assayed (LT2 and LT4,23 endothelioma murine cells b.End24 ), EA.hy926 cells appeared to give the most sensitive and reproducible response. This line is a hybrid cell type resulting from the fusion between HUVECs and the nonendothelial lung carcinoma A549/8 cell line. We first characterized the effect of thrombin on endothelial barrier function by comparing both freshly isolated HUVECs and the immortalized HUVEC cell line EA.hy926. Using a Transwell permeability system and measuring the clearance rate of a macromolecule, HRP, across endothelial cell monolayers, it was possible to quantify the phenomenon and to determine the experimental conditions under which a maximum effect of thrombin could be observed.
As shown in Fig 1
, exposure of confluent
HUVECs to
thrombin induced a concentration-dependent increase in the HRP
clearance rate. As previously reported by others,25 higher
concentrations of thrombin than those required for cell activation, as
measured by calcium entrance, were necessary to elicit HUVEC monolayer
permeability. EA.hy926 cells were found to be more responsive than
HUVECs to thrombin, as a lower concentration of the agonist was
necessary to induce maximum monolayer permeability. Responses of HUVECs
and EA.hy926 cells to thrombin were consistent with a pathway
involving the thrombin receptor. A thrombin mutant in which the
active-site serine has been replaced by an alanine (SA205 thrombin)
was inactive in inducing monolayer permeability up to 100 nmol/L, and
-thrombin, a catalytically active but proteolyzed form of
thrombin, exhibited only 40% of -thrombin activity at maximum
concentration. TRAP14 was able to mimic thrombin effects and induced a
response similar in EA.hy926 cells and in HUVECs (Fig 1). As
observed
for other cell types, 
1000 times more peptide than thrombin was
required to produce an equivalent response.
|
) or TRAP14 (
) and
EA.hy 926 cells exposed to increasing amounts of thrombin (
) or
TRAP14 (
) for 15 minutes. Values represent the mean±SEM
of four independent experiments run in triplicate.Thrombin effect on endothelial monolayer permeability was a rapid and reversible phenomenon. At maximum agonist concentration, cell retraction and gap formation were observed within 2 minutes and maximum HRP clearance rate was achieved within 15 minutes. When cells were incubated either with thrombin or TRAP14 and refed after agonist removal with culture medium containing 10% fetal calf serum, permeability to HRP rapidly decreased and restoration of the cell monolayer integrity was achieved within 3 hours.
Morphological Analysis of Endothelial
Adherence Junction Components After Thrombin Treatment
As examined by
immunofluorescence microscopy,
thrombin treatment caused endothelial cell retraction,
with the opening of intercellular gaps (see actin staining in Fig
2). The immunofluorescence staining
pattern of HUVEC (on the left) or EA.hy926 (on the right) confluent
monolayers using an anti–VE-cadherin antibody consisted of a
continuous lining at the cell borders. Under the action of thrombin, a
redistribution of VE-cadherin was observed. The antigen was strongly
detected only at contacting cell borders but redistributed in a zigzag
pattern in correspondence with intercellular gaps. The molecule was not
visible along free cell edges in areas of retraction.
|
A very similar
pattern was observed (Figs 3 and 4) for
-catenin, ß-catenin,
plakoglobin, and p120, a pp60src substrate recently shown
to be associated with the cadherin/catenin complex.26
After thrombin removal, restoration of the cell monolayer integrity
resulted in a progressive recovery of normal appearance of antigens at
junctional sites (Figs 2 through
4
).
|
|
Since EA.hy926 cells appeared to behave in a way comparable with freshly isolated HUVECs and responded to thrombin in a more sensitive and reproducible way, the experiments reported below were performed on this cell line and confirmed at least once in HUVECs.
Modification of the Composition of VE-Cadherin/Catenin Complex
by Thrombin
The organization of the VE-cadherin/catenin complex was
next
examined in cell lysates of confluent cells incubated in the presence
of 10 nmol/L (1 U/mL) thrombin for various lengths of time. Equal
aliquots of cell extracts were immunoprecipitated with VE-cadherin
antibodies, separated by SDS–polyacrylamide gel
electrophoresis, transferred to nitrocellulose membranes, and probed
with antibodies to VE-cadherin and catenins. As shown in Fig
5A, the amounts of VE-cadherin immunoprecipitated were
comparable in the control (time 0) and after various times (5, 15, and
30 minutes) of thrombin treatment. When VE-cadherin immunoprecipitates
were blotted with anti–-catenin, anti–ß-catenin,
anti-plakoglobin, or anti-p120 antibodies, the amount of each
protein associated with VE-cadherin decreased along with the duration
of thrombin treatment. The reduction was particularly significant for
plakoglobin and p120. As shown in Fig 5B, the amounts of the
four
proteins in total extracts were not significantly changed before and
after thrombin treatment. After 30 minutes of thrombin treatment and
thrombin removal (time 0 in Fig 5C), the amounts of catenins
associated
with VE-cadherin progressively increased, and the normal pattern was
achieved within 4 hours in parallel with the return to a normal
organization of cell-to-cell contacts. Comparable results, with
essentially the same timing, were obtained stimulating the cells with
500 µmol/L TRAP (data not shown).
|
Phosphorylation of Cadherin and
Catenins
Pretreatment of cell monolayers with 500 nmol/L calphostin C
(which prevents PKC activation by binding to the regulatory site of the
enzyme27 ) or 100 µmol/L H7 (a less specific PKC
inhibitor acting on the catalytic site of the
enzyme28 ) for 30 minutes prevented thrombin-induced
barrier dysfunction. Pretreatment of the cells with 1 µmol/L
staurosporine (an inhibitor of
phospholipid/calcium-dependent protein kinase29 ) for
30 minutes or with 1 µmol/L herbimycin A (a tyrosine kinase
inhibitor30 ) for 16 hours also blocked
thrombin effect on endothelial permeability. As shown
in Fig 6, the PKC inhibitor calphostin C
also prevented thrombin-induced catenin dissociation from
VE-cadherin. These observations were consistent with the mode
of signaling of the thrombin receptor31 and strongly
suggested that phosphorylation processes were required
for thrombin-induced changes in permeability.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Endothelial cell activation evoked by thrombin is associated with a dramatic alteration of cell morphology, with cell contraction and formation of interendothelial gaps.32 The parallel increase in endothelial cell monolayer permeability is apparent within a few minutes and is reversible.33 Thrombin receptor proteolysis is a prerequisite for cellular activation.25 34 Accumulating evidence suggests that both increased cytosolic calcium- and diacylglycerol-induced activation of PKC are critical for the subsequent alteration of endothelial barrier function.35 36 cAMP and cGMP act as potent fine regulators of endothelial permeability.37
The mechanism involved in endothelial cell retraction has not been fully clarified. It has been suggested that cell shape changes may result from an active cellular contraction event associated with activation of myosin light chain kinase and phosphorylation of myosin light chain.38 39 40 However, as the rapid decrease in the level of phosphorylated myosin light chain does not correlate with the much slower return to normal barrier function, after increases in centripetal forces via rapid myosin light chain phosphorylation, additional mechanisms such as reduced cell-matrix or intercellular adhesive forces may maintain the gap-producing state and cell-to-cell detachment. Both PKC and calcium are required for the full thrombin effect. Although it is a potent inducer of myosin light chain phosphorylation in bovine smooth muscle cells, phorbol 12-myristate 13-acetate does not increase myosin light chain phosphorylation above constitutive levels in either bovine pulmonary artery ECs or HUVECs. Thus, unlike smooth muscle cells, PKC does not directly lead to myosin light chain phosphorylation in endothelial cells, and additional myosin light chain independent mechanisms, such as reduced cell-to-cell or cell-to-matrix adhesion, must exist by which PKC accomplishes altered cytoskeletal protein interactions, intercellular gap formation, and endothelial cell barrier dysfunction.
Their high order of structure makes adherence-type junctions major targets for downregulation of intercellular contacts. VE-cadherin is the only cadherin found consistently at the interendothelial contacts in all type of vessels.12 N-cadherin, the other major cadherin in human endothelial cells, is mostly diffuse on the cell membrane.41 P-cadherin is expressed at a low amount, and E-cadherin has been found only in brain vessels.42 Highly associated with the cytoplasmic domain of cadherins, catenins might represent important regulatory proteins for the extracellular adhesive properties of cadherins.
In this paper, we show that thrombin induces disassembly of
adherence junctions in a way related to the increase in permeability.
In immunofluorescence, thrombin caused the
disappearance of VE-cadherin and catenins (-catenin,
ß-catenin, plakoglobin, and p120) at cell-to-cell
retraction sites. In addition, immunoprecipitation
analysis showed that lower amounts of the four catenins were
associated to VE-cadherin. These effects had the same time course and
reversibility as the increase in monolayer permeability. Activation of
PKC seemed to be required for these changes, since calphostin C, which
competes at the binding site for diacylglycerol, was able to prevent
both the increase in monolayer permeability induced by thrombin and
catenin dissociation from VE-cadherin.
The mechanisms regulating adherence-junction organization are
largely unknown in endothelial cells. Decrease in
calcium concentration in culture medium induced a rapid disappearance
of VE-cadherin and catenins at cell junctions.7 This
disappearance was not accompanied by a dissociation of the
cadherin/catenin complex and was most likely due to a change in
VE-cadherin conformation and adhesive properties. In addition,
endothelial cell adherence junctions can be slowly
modified by the state of confluence of the cells.13 In
subconfluent cells, VE-cadherin, -catenins, and ß-catenins
were found at the junctions, but plakoglobin and actin microfilaments
were associated with these structures only at later stages of junction
maturation.
Thrombin is the first agent we know able to cause a general rapid and reversible disassembly of the VE-cadherin/catenin complex. The mechanism of this effect remains to be fully defined. The dissociation of catenins from VE-cadherin was not accompanied by detectable changes in the total amount of these molecules in the cytoplasm, which suggests that catenins and VE-cadherin remain protected from degradation and are possibly capable of a rapid turnover at cell-to-cell junctions. Indeed, the thrombin effect was reversible, and a complete reassembly of VE-cadherin/catenin complex was apparent within a few hours.
Growth factors or Src overexpression in other cell types induces tyrosine phosphorylation of cadherins and catenins, accompanied by a decrease in cell-to-cell adhesion.10 43 Particularly high levels of tyrosine-specific phosphorylation, as well as elevated levels of pp60Src44 and activation of pp125FAK,45 have been detected under stimulation by thrombin in the platelet system, where rapid cytoskeletal modifications are crucial for shape change. Tyrosine phosphorylation may also play a role in the thrombin-induced morphological changes, such as membrane and cytoskeletal rearrangements, observed in endothelial cells. However, in preliminary experiments (M.J.R., unpublished data, 1995), although thrombin-induced endothelial permeability was inhibited by tyrosine kinase inhibitors, we did not observe any significant increase in tyrosine phosphorylation of VE-cadherin and associated catenins. Further work is needed regarding cellular signals regulating junction assembly as well as eventual additional molecular participants.
In conclusion, we characterized at a molecular level some of the events associated with cell-to-cell retraction induced by thrombin on endothelial cells. The disassembly of adherence-junction components induced by this agent might contribute to the increase in endothelial permeability observed after its administration to cultured cells. The relevance of these observations in vivo remains to be established. Besides adherence junctions, in many regions of the vascular tree, endothelial cells present tight junctions,46 47 and we do not know whether thrombin stimulation could alter the architecture of these organelles. Adherence-junction organization, however, is required for tight-junction assembly,48 suggesting that alterations of these structures could have a more general effect on endothelial permeability.
|
Selected Abbreviations and Acronyms |
|---|
|
|
Acknowledgments |
|---|
This work was supported in part by Programme d'actions intégrées franco-italien Galilee (Ministère des affaires étrangères, France).
Received September 11, 1995; accepted November 22, 1995.
|
References |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
1. Garcia JGN, Perlman MB, Johnson A, Ferro T, Jubiz W, Malik AB. Inflammatory events following fibrin microembolization: alteration in alveolar macrophage and neutrophil function. Am Rev Respir Dis. 1988;137:630-635. [Medline] [Order article via Infotrieve]
2. Ross R, Glomset J. The pathogenesis of atherosclerosis. N Engl J Med. 1976;5:420-423.
3. Garcia JGN, Aschner JL, Malik AB. Regulation of thrombin-induced endothelial barrier dysfunction and prostaglandin synthesis. In: Berliner LJ, ed. Thrombin: Structure and Function. New York, NY: Plenum Press; 1992:397-430.
4. Malik AB, Fenton JW. Thrombin-mediated increase in vascular endothelial permeability. Semin Thromb Hemost. 1992;18:193-199.[Medline] [Order article via Infotrieve]
5. Tsukita S, Tsukita S, Nagafuchi A, Yonemura S. Molecular linkage between cadherins and actin filaments in cell-cell adherens junctions. Curr Opin Cell Biol. 1992;4:834-839. [Medline] [Order article via Infotrieve]
6. Geiger B, Ayalon O. Cadherins. Annu Rev Cell Biol. 1992;8:307-332.
7. Dejana E, Corada M, Lampugnani MG. Endothelial cell to cell junctions. FASEB J. 1995;9:910-918. [Abstract]
8. Kemler R. From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion. Trends Genet. 1993;9:317-321. [Medline] [Order article via Infotrieve]
9.
Takeichi M. Cadherin cell adhesion receptors as
morphogenic regulators. Science. 1991;251:1451-1455.
10. Hinck L, Nõthke IS, Papkoff J, Nelson WJ. ß-Catenin: a common target for the regulation of cell adhesion by Wnt-1 and Src signaling pathways. Trends Biochem Sci. 1994;19:538-542. [Medline] [Order article via Infotrieve]
11. Suzuki S, Sano K, Tanihara H. Diversity of the cadherin family: evidence for eight new cadherins in nervous tissue. Cell Regul. 1991;2:261-270. [Medline] [Order article via Infotrieve]
12.
Lampugnani MG, Resnati M, Raiteri M, Pigott R, Pisacane
A, Houen G, Ruco LP, Dejana E. A novel
endothelial-specific membrane protein is a marker
of cell-cell contacts. J Cell Biol. 1992;118:1511-1522.
13.
Lampugnani MG, Corada M, Caveda L, Breviario F, Dejana
E. The molecular organization of endothelial
cell to cell junctions: differential association of plakoglobin,
ß-catenin and -catenin to vascular
endothelial cadherin (VE-cadherin).
J Cell Biol. 1995;129:203-217.
14. Barbieri B, Balconi G, Dejana E, Donati MB. Evidence that vascular endothelial cells can induce the retraction of fibrin clot. Proc Soc Exp Biol Med. 1981;168:204-207. [Medline] [Order article via Infotrieve]
15.
Edgell CJS, McDonald CC, Graham JB. Permanent
cell line expressing factor VIII related antigen established by
hybridization. Proc Natl Acad Sci U S A. 1983;80:3734-3737.
16.
Bezeaud A, Denninger MH, Guillin MC. Interaction
of human thrombin and thrombin with antithrombin III, protein C
and thrombomodulin. Eur J Biochem. 1985;153:491-496. [Medline]
[Order article via Infotrieve]
17. Plantier JL, Berthier R, Rival Y, Schweitzer A, Rabiet MJ. Evidence for a selective inhibitory effect of thrombin on megakaryocyte progenitor growth mediated by the thrombin receptor. Br J Haematol. 1994;87:755-762. [Medline] [Order article via Infotrieve]
18. Vu TKH, Hung DT, Wheaton VI, Coughlin SR. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell. 1991;89:351-355.
19. Langeler EG, Van Hinsbergh VWM. Characterization of an in vitro model to study the permeability of human arterial endothelial cell monolayers. Thromb Haemost. 1988;60:240-246. [Medline] [Order article via Infotrieve]
20. Ortiz de Montellano PR, David SK, Ator M, Tew D. Mechanism-based inactivation of horseradish peroxidase by sodium azide: formation of meso-azidoprotoporphyrin IX. Biochemistry. 1988;27:5470-5476. [Medline] [Order article via Infotrieve]
21.
Lampugnani MG, Resnati M, Dejana E, Marchisio
PC. The role of integrins in the maintenance of
endothelial monolayer integrity. J
Cell Biol. 1991;112:479-490.
22.
Laposata M, Dovnarsky D, Shin H.
Thrombin-induced gap formation in confluent
endothelial cell monolayers in vitro.
Blood. 1983;62:549-556.
23. Green DR, Banuls MP, Gearing AJH, Needham LA, White MRH, Clements JM. Generation of human umbilical vein endothelial cell lines which maintain their differentiated phenotype. Endothelium. 1994;2:191-201.
24. Williams RL, Risau W, Zerwes HG, Drexler H, Aguzzi A, Wagner EF. Endothelioma cells expressing the polyoma middle T oncogene induce hemangiomas by host cell recruitment. Cell. 1989;57:1053-1063. [Medline] [Order article via Infotrieve]
25. Garcia JGN, Patterson C, Bahler C, Aschner J, Hart CM, English D. Thrombin receptor activating peptides induce Ca2+ mobilization, barrier dysfunction, prostaglandin synthesis, and platelet-derived growth factor mRNA expression in cultured endothelium. J Cell Physiol. 1993;156:541-549. [Medline] [Order article via Infotrieve]
26.
Staddon JM, Smales C, Schulze C, Esch F, Rubin
LL. p120, a p120-related protein (p100), and the
cadherin/catenin complex. J Cell Biol. 1995;130:369-381.
27. Kobayashi E, Nakano H, Morimoto M, Tamaoki T. Calphostin C (HCN-1028C), a novel microbial compound, is a highly potent and specific inhibitor of protein kinase C. Biochem Biophys Res Commun. 1989;176:288-293.
28. Gescher A. Towards selective pharmacological modulation of protein kinase C. Br J Cancer. 1992;66:10-19. [Medline] [Order article via Infotrieve]
29. Tamaoki T, Nomoto H, Takahashi I, Kato Y, Morimoto M, Tomita F. Staurosporine, a potent inhibitor of phospholipid/Ca++ dependent protein kinase. Biochem Biophys Res Commun. 1986;135:397-402. [Medline] [Order article via Infotrieve]
30.
Satoh T, Uehara Y, Kasiro Y. Inhibition of
interleukin 3 and granulocyte-macrophage
colony–stimulating factor stimulated increase of active
ras-GTP by herbimycin A, a specific inhibitor of
tyrosine kinases. J Biol Chem. 1992;267:2537-2541.
31. Van Obberghen-Schilling E, Pouysségur J. Signalling pathways of the thrombin receptor. In: Zucker M, ed. Thrombosis and Haemostasis 1993 State of the Art. Stuttgart, Germany: Schattauer; 1993:163-167.
32. Garcia JGN, Birnboim AS, Bizios R, Del Vecchio PJ, Fenton JW, Malik AB. Thrombin-induced increases in albumin clearance across cultured endothelial monolayers. J Cell Physiol. 1986;128:96-104. [Medline] [Order article via Infotrieve]
33. Lum H, Ashner JL, Phillips PG, Fletcher PW, Malik AB. Time course of thrombin-induced increase in endothelial permeability: relationship to Ca++ and inositol polyphosphates. Am J Physiol. 1992;7:L219-L225.
34.
Aschner JL, Lennon JM, Fenton JW, Ashner M, Malik
AB. Enzymatic activity is necessary for thrombin-mediated
increase in endothelial permeability. Am
J Physiol. 1990;259:L270-L275.
35. Lynch J, Ferro TJ, Blumenstock FA, Brockenauer AM, Malik AB. Increased endothelial permeability is mediated by protein kinase C activation. J Clin Invest. 1990;85:1991-1998.
36.
Stasek JE, Garcia JGN. The role of protein
kinase C in -thrombin–mediated endothelial
cell activation. Semin Thromb Hemost. 1992;18:117-125. [Medline]
[Order article via Infotrieve]
37. Westendorp RG, Draijer R, Meinders AE, van Hinsbergh VW. Cyclic-GMP–mediated increase in permeability of human umbilical and pulmonary artery endothelial cell monolayers. J Vasc Res. 1994;31:42-51. [Medline] [Order article via Infotrieve]
38.
Schnittler HJ, Wilke A, Gress T, Suttorp N, Drenckahn
D. Role of actin and myosin in the control of paracellular
permeability in pig, rat and human vascular endothelium. J
Physiol (Lond). 1990;431:379-401.
39.
Wysolmerski RB, Lagunoff D. Regulation of
permeabilized endothelial cell
retraction by myosin phosphorylation. Am
J Physiol. 1991;261:C32-C40.
40. Garcia JGN, Davis HW, Patterson CE. Regulation of endothelial cell gap formation and barrier dysfunction: role of myosin light chain phosphorylation. J Cell Physiol. 1995;163:510-522. [Medline] [Order article via Infotrieve]
41.
Salomon D, Ayalon O, Patel-King R, Hynes RO, Geiger
B. Extrajunctional distribution of N-cadherin in cultured human
endothelial cells. J Cell
Sci. 1992;102:1-11.
42. Liaw CV, Cannon C, Power MD, Kiboneta PK, Rubin LL. Identification and cloning of two species of cadherins in bovine endothelial cells. EMBO J. 1990;9:2701-2708. [Medline] [Order article via Infotrieve]
43.
Hoschuetzky H, Aberle H, Kemler R. ß-Catenin
mediates the interaction of the cadherin-catenin complex with
epidermal growth factor receptor. J Cell
Biol. 1994;127:1375-1380.
44.
Golden A, Brugge JS. Thrombin treatment induces
rapid changes in tyrosine phosphorylation in
platelets. Proc Natl Acad Sci U S A. 1989;86:901-905.
45.
Shaller MD, Borgman CA, Cobb BS, Vines RR, Reynolds AB,
Parson JT. pp125FAK, a structurally
distinctive protein-tyrosine kinase associated with focal
adhesions. Proc Natl Acad Sci U S A. 1992;89:5192-5196.
46. Simionescu M, Simionescu N. Endothelial transport macromolecules: transcytosis and endocytosis. Cell Biol Rev. 1991;25:5-80. [Medline] [Order article via Infotrieve]
47. Rubin LL. Endothelial cells: adhesion and tight junctions. Curr Opin Cell Biol. 1992;4:830-833. [Medline] [Order article via Infotrieve]
48.
Meyer RA, Laird DW, Revel JP, Johnson RG.
Inhibition of gap junction and adherens junction assembly by connexin
and A-CAM antibodies. J Cell Biol. 1992;119:179-189.
This article has been cited by other articles:
 |
|
 |
|
  J. I. Borissoff, H. M.H. Spronk, S. Heeneman, and H. ten Cate Is thrombin a key player in the 'coagulation-atherogenesis' maze? Cardiovasc Res, June 1, 2009; 82(3): 392 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-M. Heupel, A. Efthymiadis, N. Schlegel, T. Muller, Y. Baumer, W. Baumgartner, D. Drenckhahn, and J. Waschke Endothelial barrier stabilization by a cyclic tandem peptide targeting VE-cadherin transinteraction in vitro and in vivo J. Cell Sci., May 15, 2009; 122(10): 1616 - 1625. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Yang Gu, D. F. Lewis, J. S. Alexander, and Yuping Wang Placenta-derived Chymotrypsin-like Protease (CLP) Disturbs Endothelial Junctional Structure in Preeclampsia Reproductive Sciences, May 1, 2009; 16(5): 479 - 488. [Abstract] [PDF]
|
|
|
|
 |
|
 R. Ramchandran, D. Mehta, S. M. Vogel, M. K. Mirza, P. Kouklis, and A. B. Malik Critical role of Cdc42 in mediating endothelial barrier protection in vivo Am J Physiol Lung Cell Mol Physiol, August 1, 2008; 295(2): L363 - L369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Ponnuchamy and R. A. Khalil Role of ADAMs in Endothelial Cell Permeability: Cadherin Shedding and Leukocyte Rolling Circ. Res., May 23, 2008; 102(10): 1139 - 1142. [Full Text] [PDF]
|
|
|
|
|
|
B. Schulz, J. Pruessmeyer, T. Maretzky, A. Ludwig, C. P. Blobel, P. Saftig, and K. Reiss ADAM10 Regulates Endothelial Permeability and T-Cell Transmigration by Proteolysis of Vascular Endothelial Cadherin Circ. Res., May 23, 2008; 102(10): 1192 - 1201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. E. Dewi, T. Takasaki, and I. Kurane Peripheral blood mononuclear cells increase the permeability of dengue virus-infected endothelial cells in association with downregulation of vascular endothelial cadherin J. Gen. Virol., March 1, 2008; 89(3): 642 - 652. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Vestweber VE-Cadherin: The Major Endothelial Adhesion Molecule Controlling Cellular Junctions and Blood Vessel Formation Arterioscler. Thromb. Vasc. Biol., February 1, 2008; 28(2): 223 - 232. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. B. Carter, G. Niu, M. D. Ward, G. Small, J. E. Hahn, and B. J. Muffly Mechanisms of HER2-Induced Endothelial Cell Retraction Ann. Surg. Oncol., October 1, 2007; 14(10): 2971 - 2978. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Su, M. Hodnett, N. Wu, A. Atakilit, C. Kosinski, M. Godzich, X. Z. Huang, J. K. Kim, J. A. Frank, M. A. Matthay, et al. Integrin {alpha}vbeta5 Regulates Lung Vascular Permeability and Pulmonary Endothelial Barrier Function Am. J. Respir. Cell Mol. Biol., March 1, 2007; 36(3): 377 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Uchide, M. Sakon, H. Ariyoshi, S. Nakamori, M. Tokunaga, and M. Monden Cancer Cells Cause Vascular Endothelial Cell (vEC) Retraction via 12(S)HETE Secretion; The Possible Role of Cancer Cell Derived Microparticle Ann. Surg. Oncol., February 1, 2007; 14(2): 862 - 868. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Mehta and A. B. Malik Signaling Mechanisms Regulating Endothelial Permeability Physiol Rev, January 1, 2006; 86(1): 279 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. McLaughlin, L. Shen, M. Holinstat, J. D. Brooks, E. DiBenedetto, and H. E. Hamm Functional Selectivity of G Protein Signaling by Agonist Peptides and Thrombin for the Protease-activated Receptor-1 J. Biol. Chem., July 1, 2005; 280(26): 25048 - 25059. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hudry-Clergeon, D. Stengel, E. Ninio, and I. Vilgrain Platelet-activating factor increases VE-cadherin tyrosine phosphorylation in mouse endothelial cells and its association with the PtdIns3'-kinase FASEB J, April 1, 2005; 19(6): 512 - 520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Lambeng, Y. Wallez, C. Rampon, F. Cand, G. Christe, D. Gulino-Debrac, I. Vilgrain, and P. Huber Vascular Endothelial-Cadherin Tyrosine Phosphorylation in Angiogenic and Quiescent Adult Tissues Circ. Res., February 18, 2005; 96(3): 384 - 391. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Li, C. N. Hahn, M. Parsons, J. Drew, M. A. Vadas, and J. R. Gamble Role of protein kinase C{zeta} in thrombin-induced endothelial permeability changes: inhibition by angiopoietin-1 Blood, September 15, 2004; 104(6): 1716 - 1724. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Bazzoni and E. Dejana Endothelial Cell-to-Cell Junctions: Molecular Organization and Role in Vascular Homeostasis Physiol Rev, July 1, 2004; 84(3): 869 - 901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Kouklis, M. Konstantoulaki, S. Vogel, M. Broman, and A. B. Malik Cdc42 Regulates the Restoration of Endothelial Barrier Function Circ. Res., February 6, 2004; 94(2): 159 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Minami, A. Sugiyama, S.-Q. Wu, R. Abid, T. Kodama, and W. C. Aird Thrombin and Phenotypic Modulation of the Endothelium Arterioscler. Thromb. Vasc. Biol., January 1, 2004; 24(1): 41 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Guo, M. H. Wu, H. J. Granger, and S. Y. Yuan Transference of recombinant VE-cadherin cytoplasmic domain alters endothelial junctional integrity and porcine microvascular permeability J. Physiol., January 1, 2004; 554(1): 78 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kataoka, J. R. Hamilton, D. D. McKemy, E. Camerer, Y.-W. Zheng, A. Cheng, C. Griffin, and S. R. Coughlin Protease-activated receptors 1 and 4 mediate thrombin signaling in endothelial cells Blood, November 1, 2003; 102(9): 3224 - 3231. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Konstantoulaki, P. Kouklis, and A. B. Malik Protein kinase C modifications of VE-cadherin, p120, and {beta}-catenin contribute to endothelial barrier dysregulation induced by thrombin Am J Physiol Lung Cell Mol Physiol, August 1, 2003; 285(2): L434 - L442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H. Adamson, M. Zeng, G. N. Adamson, J. F. Lenz, and F. E. Curry PAF- and bradykinin-induced hyperpermeability of rat venules is independent of actin-myosin contraction Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H406 - H417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. O. Harrington, J. L. Brunelle, C. J. Shannon, E. S. Kim, K. Mennella, and S. Rounds Role of Protein Kinase C Isoforms in Rat Epididymal Microvascular Endothelial Barrier Function Am. J. Respir. Cell Mol. Biol., May 1, 2003; 28(5): 626 - 636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Hermant, S. Bibert, E. Concord, B. Dublet, M. Weidenhaupt, T. Vernet, and D. Gulino-Debrac Identification of Proteases Involved in the Proteolysis of Vascular Endothelium Cadherin during Neutrophil Transmigration J. Biol. Chem., April 11, 2003; 278(16): 14002 - 14012. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Quadri, M. Bhattacharjee, K. Parthasarathi, T. Tanita, and J. Bhattacharya Endothelial Barrier Strengthening by Activation of Focal Adhesion Kinase J. Biol. Chem., April 4, 2003; 278(15): 13342 - 13349. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. C. Albuquerque and A. S. Flozak Wound Closure in Sheared Endothelial Cells Is Enhanced by Modulation of Vascular Endothelial-Cadherin Expression and Localization Experimental Biology and Medicine, December 1, 2002; 227(11): 1006 - 1016. [Abstract] [Full Text]
|
|
|
|
 |
|
 Y. Wang, Y. Gu, and M. J. Lucas Expression of Thrombin Receptors in Endothelial Cells and Neutrophils from Normal and Preeclamptic Pregnancies J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3728 - 3734. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Salter, C. F. Krieglstein, A. C. Issekutz, and D. N. Granger Platelets modulate ischemia/reperfusion-induced leukocyte recruitment in the mesenteric circulation Am J Physiol Gastrointest Liver Physiol, December 1, 2001; 281(6): G1432 - G1439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Tiruppathi, T. Naqvi, R. Sandoval, D. Mehta, and A. B. Malik Synergistic effects of tumor necrosis factor-{alpha} and thrombin in increasing endothelial permeability Am J Physiol Lung Cell Mol Physiol, October 1, 2001; 281(4): L958 - L968. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Macfarlane, M. J. Seatter, T. Kanke, G. D. Hunter, and R. Plevin Proteinase-Activated Receptors Pharmacol. Rev., June 1, 2001; 53(2): 245 - 282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Sandoval, A. B. Malik, T. Naqvi, D. Mehta, and C. Tiruppathi Requirement for Ca2+ signaling in the mechanism of thrombin-induced increase in endothelial permeability Am J Physiol Lung Cell Mol Physiol, February 1, 2001; 280(2): L239 - L247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B Wojciak-Stothard, S Potempa, T Eichholtz, and A. Ridley 9Rgr; and Rac but not Cdc42 regulate endothelial cell permeability J. Cell Sci., January 4, 2001; 114(7): 1343 - 1355. [Abstract] [PDF]
|
|
|
|
 |
|
 S. M. VOGEL, X. GAO, D. MEHTA, R. D. YE, T. A. JOHN, P. ANDRADE-GORDON, C. TIRUPPATHI, and A. B. MALIK Abrogation of thrombin-induced increase in pulmonary microvascular permeability in PAR-1 knockout mice Physiol Genomics, December 18, 2000; 4(2): 137 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Groten, R. Kreienberg, I. Fialka, L. Huber, and D. Wedlich Altered subcellular distribution of cadherin-5 in endothelial cells caused by the serum of pre-eclamptic patients Mol. Hum. Reprod., November 1, 2000; 6(11): 1027 - 1032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Gamble, J. Drew, L. Trezise, A. Underwood, M. Parsons, L. Kasminkas, J. Rudge, G. Yancopoulos, and M. A. Vadas Angiopoietin-1 Is an Antipermeability and Anti-Inflammatory Agent In Vitro and Targets Cell Junctions Circ. Res., September 29, 2000; 87(7): 603 - 607. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Minshall, C. Tiruppathi, S. M. Vogel, W. D. Niles, A. Gilchrist, H. E. Hamm, and A. B. Malik Endothelial Cell-surface gp60 Activates Vesicle Formation and Trafficking via Gi-coupled Src Kinase Signaling Pathway J. Cell Biol., September 5, 2000; 150(5): 1057 - 1070. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Ukropec, M. K. Hollinger, S. M. Salva, and M. J. Woolkalis SHP2 Association with VE-Cadherin Complexes in Human Endothelial Cells Is Regulated by Thrombin J. Biol. Chem., February 25, 2000; 275(8): 5983 - 5986. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C Johnson-Leger, M Aurrand-Lions, and B. Imhof The parting of the endothelium: miracle, or simply a junctional affair? J. Cell Sci., January 3, 2000; 113(6): 921 - 933. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Corada, M. Mariotti, G. Thurston, K. Smith, R. Kunkel, M. Brockhaus, M. G. Lampugnani, I. Martin-Padura, A. Stoppacciaro, L. Ruco, et al. Vascular endothelial-cadherin is an important determinant of microvascular integrity in vivo PNAS, August 17, 1999; 96(17): 9815 - 9820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Underwood, C. G. Murphy, J. Chen, L. Franse-Carman, I. Wood, D. L. Epstein, and J. A. Alvarado Glucocorticoids regulate transendothelial fluid flow resistance and formation of intercellular junctions Am J Physiol Cell Physiol, August 1, 1999; 277(2): C330 - C342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Trottein, L. Descamps, S. Nutten, M.-P. Dehouck, V. Angeli, A. Capron, R. Cecchelli, and M. Capron Schistosoma mansoni Activates Host Microvascular Endothelial Cells To Acquire an Anti-Inflammatory Phenotype Infect. Immun., July 1, 1999; 67(7): 3403 - 3409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. W. Hauck, C. Schulz, A. Schomig, R. K. Hoffman, and R. A. Panettieri Jr. alpha -Thrombin stimulates contraction of human bronchial rings by activation of protease-activated receptors Am J Physiol Lung Cell Mol Physiol, July 1, 1999; 277(1): L22 - L29. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Vouret-Craviari, D. Grall, G. Flatau, J. Pouyssegur, P. Boquet, and E. Van Obberghen-Schilling Effects of Cytotoxic Necrotizing Factor 1 and Lethal Toxin on Actin Cytoskeleton and VE-Cadherin Localization in Human Endothelial Cell Monolayers Infect. Immun., June 1, 1999; 67(6): 3002 - 3008. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Hurst IV, P. L. Goldberg, F. L. Minnear, R. L. Heimark, and P. A. Vincent Rearrangement of adherens junctions by transforming growth factor-beta 1: role of contraction Am J Physiol Lung Cell Mol Physiol, April 1, 1999; 276(4): L582 - L595. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Hordijk, E Anthony, F. Mul, R Rientsma, L. Oomen, and D Roos Vascular-endothelial-cadherin modulates endothelial monolayer permeability J. Cell Sci., January 6, 1999; 112(12): 1915 - 1923. [Abstract] [PDF]
|
|
|
|
|
|
G. P. v. N. Amerongen, R. Draijer, M. A. Vermeer, and V. W. M. van Hinsbergh Transient and Prolonged Increase in Endothelial Permeability Induced by Histamine and Thrombin : Role of Protein Kinases, Calcium, and RhoA Circ. Res., November 30, 1998; 83(11): 1115 - 1123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Essler, K. Hermann, M. Amano, K. Kaibuchi, J. Heesemann, P. C. Weber, and M. Aepfelbacher Pasteurella multocida Toxin Increases Endothelial Permeability via Rho Kinase and Myosin Light Chain Phosphatase J. Immunol., November 15, 1998; 161(10): 5640 - 5646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Gulino, E. Delachanal, E. Concord, Y. Genoux, B. Morand, M.-O. Valiron, E. Sulpice, R. Scaife, M. Alemany, and T. Vernet Alteration of Endothelial Cell Monolayer Integrity Triggers Resynthesis of Vascular Endothelium Cadherin J. Biol. Chem., November 6, 1998; 273(45): 29786 - 29793. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Vouret-Craviari, P. Boquet, J. Pouysségur, and E. Van Obberghen-Schilling Regulation of the Actin Cytoskeleton by Thrombin in Human Endothelial Cells: Role of Rho Proteins in Endothelial Barrier Function Mol. Biol. Cell, September 1, 1998; 9(9): 2639 - 2653. [Abstract] [Full Text]
|
|
|
|
|
|
M. Essler, M. Amano, H.-J. Kruse, K. Kaibuchi, P. C. Weber, and M. Aepfelbacher Thrombin Inactivates Myosin Light Chain Phosphatase via Rho and Its Target Rho Kinase in Human Endothelial Cells J. Biol. Chem., August 21, 1998; 273(34): 21867 - 21874. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Saito, Y. Minamiya, M. Kitamura, S. Saito, K. Enomoto, K. Terada, and J.-i. Ogawa Endothelial Myosin Light Chain Kinase Regulates Neutrophil Migration Across Human Umbilical Vein Endothelial Cell Monolayer J. Immunol., August 1, 1998; 161(3): 1533 - 1540. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Herren, B. Levkau, E. W. Raines, and R. Ross Cleavage of beta -Catenin and Plakoglobin and Shedding of VE-Cadherin during Endothelial Apoptosis: Evidence for a Role for Caspases and Metalloproteinases Mol. Biol. Cell, June 1, 1998; 9(6): 1589 - 1601. [Abstract] [Full Text]
|
|
|
|
|
|
S Esser, M. Lampugnani, M Corada, E Dejana, and W Risau Vascular endothelial growth factor induces VE-cadherin tyrosine phosphorylation in endothelial cells J. Cell Sci., January 7, 1998; 111(13): 1853 - 1865. [Abstract] [PDF]
|
|
|
|
|
|
R. A. Henriksen, G. P. Samokhin, and P. B. Tracy Thrombin-Induced Thromboxane Synthesis by Human Platelets : Properties of an Anion Binding Exosite I– Independent Receptor Arterioscler. Thromb. Vasc. Biol., December 1, 1997; 17(12): 3519 - 3526. [Abstract] [Full Text]
|
|
|
|
|
|
V. W.M. van Hinsbergh Endothelial Permeability for Macromolecules: Mechanistic Aspects of Pathophysiological Modulation Arterioscler. Thromb. Vasc. Biol., June 1, 1997; 17(6): 1018 - 1023. [Full Text]
|
|
|
|
|
|
M. Lampugnani, M Corada, P Andriopoulou, S Esser, W Risau, and E Dejana Cell confluence regulates tyrosine phosphorylation of adherens junction components in endothelial cells J. Cell Sci., January 9, 1997; 110(17): 2065 - 2077. [Abstract] [PDF]
|
|
|
|
|
|
A. Gilchrist, J. F. Vanhauwe, A. Li, T. O. Thomas, T. Voyno-Yasenetskaya, and H. E. Hamm Galpha Minigenes Expressing C-terminal Peptides Serve as Specific Inhibitors of Thrombin-mediated Endothelial Activation J. Biol. Chem., July 6, 2001; 276(28): 25672 - 25679. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||