How the protease thrombin talks to cells

Coughlin, Shaun R.

doi:10.1073/pnas.96.20.11023

Cited by 547 publications

(440 citation statements)

References 65 publications

Supporting

Mentioning

430

Contrasting

Unclassified

Order By: Relevance

“…This protease converts circulating fibrinogen to fibrin monomer, which polymerizes to form fibrin, the fibrous matrix of blood clot. Besides this essential role in coagulation, thrombin also elicits cell activation acting like a traditional hormone (Coughlin, 1999). In endothelial cells, thrombin causes vWF release, the appearance of P-selectin at the plasma membrane, production of PAF and chemokines.…”

Section: Coagulation and Fibrinolysismentioning

confidence: 99%

Endothelial cell functions

Michiels

2003

Journal Cellular Physiology

621

429

View full text Add to dashboard Cite

Endothelial cells play a wide variety of critical roles in the control of vascular function. Indeed, since the early 1980s, the accumulating knowledge of the endothelial cell structure as well as of the functional properties of the endothelial cells shifted their role from a passive membrane or barrier to a complex tissue with complex functions adaptable to needs specific in time and location. Hence, it participates to all aspects of the vascular homeostasis but also to physiological or pathological processes like thrombosis, inflammation, or vascular wall remodeling. Some of the most important endothelial functions will be described in the following review and more specifically, their role in blood vessel formation, in coagulation and fibribolysis, in the regulation of vascular tone as well as their participation in inflammatory reactions and in tumor neoangiogenesis. J. Cell. Physiol. 196: 430–443, 2003. © 2003 Wiley‐Liss, Inc.

show abstract

Section: Coagulation and Fibrinolysismentioning

confidence: 99%

Endothelial cell functions

Michiels

2003

Journal Cellular Physiology

621

429

View full text Add to dashboard Cite

show abstract

“…Thrombin exerts many of its actions through protease-activated receptors (PAR) (8,9). Thrombin activates at least three members of this family of receptors, namely PAR-1, PAR-3, and PAR-4.…”

mentioning

confidence: 99%

Thrombin Induces Mast Cell Adhesion to Fibronectin: Evidence for Involvement of Protease-Activated Receptor-1

Vliagoftis

2002

The Journal of Immunology

View full text Add to dashboard Cite

Thrombin activates mast cells to release inflammatory mediators through a mechanism involving protease-activated receptor-1 (PAR-1). We hypothesized that PAR-1 activation would induce mast cell adhesion to fibronectin (FN). Fluorescent adhesion assay was performed in 96-well plates coated with FN (20 μg/ml). Murine bone marrow cultured mast cells (BMCMC) were used after 3–5 wk of culture (>98% mast cells by flow cytometry for c-Kit expression). Thrombin induced β-hexosaminidase, IL-6, and matrix metalloproteinase-9 release from BMCMC. Thrombin and the PAR-1-activating peptide AparafluoroFRCyclohexylACitY-NH2 (cit) induced BMCMC adhesion to FN in a dose-dependent fashion, while the PAR-1-inactive peptide FSLLRY-NH2 had no effect. Thrombin and cit induced also BMCMC adhesion to laminin. Thrombin-mediated adhesion to FN was inhibited by anti-α5 integrin Ab (51.1 ± 6.7%; n = 5). The combination of anti-α5 and anti-α4 Abs induced higher inhibition (65.7 ± 7.1%; n = 5). Unlike what is known for FcεRI-mediated adhesion, PAR-1-mediated adhesion to FN did not increase mediator release. We then explored the signaling pathways involved in PAR-1-mediated mast cell adhesion. Thrombin and cit induced p44/42 and p38 phosphorylation. Pertussis toxin inhibited PAR-1-mediated BMCMC adhesion by 57.3 ± 7.3% (n = 4), indicating that Gi proteins are involved. Wortmannin and calphostin almost completely inhibited PAR-1-mediated mast cell adhesion, indicating that PI-3 kinase and protein kinase C are involved. Adhesion was partially inhibited by the mitogen-activated protein kinase kinase 1/2 inhibitor U0126 (24.5 ± 3.3%; n = 3) and the p38 inhibitor SB203580 (25.1 ± 10.4%; n = 3). The two inhibitors had additive effects. Therefore, thrombin mediates mast cell adhesion through the activation of Gi proteins, phosphoinositol 3-kinase, protein kinase C, and mitogen-activated protein kinase pathways.

show abstract

“…Thrombin activates platelets through cell surface receptors known as protease-activated receptors (PARs) [8]. PARs belong to the class of seven transmembrane domain G proteincoupled receptors.…”

Section: Introductionmentioning

confidence: 99%

Characterization of a new peptide agonist of the protease-activated receptor-1

Mao

Jin

Kunapuli

2008

Biochemical Pharmacology

View full text Add to dashboard Cite

A new peptide (TFRRRLSRATR), from the c-terminal of human platelet P2Y 1 receptor, was synthesized and its biological function was evaluated. This peptide activated platelets in a concentration-dependent manner, causing shape change, aggregation, secretion and calcium mobilization. Of the several receptor antagonists tested, only BMS200261, a PAR-1 specific antagonist, totally abolished the peptide-induced platelet aggregation, secretion and calcium mobilization. The TFRRR-peptide-pretreated washed platelets failed to aggregate in response to SFLLRN (10 μM) but not to AYPGKF (500 μM). In addition, in mouse platelets, peptide concentrations up to 600 μM failed to cause platelet activation, indicating that the TFRRR-peptide activated platelets through the PAR-1 receptor rather than through the PAR-4 receptor. The shape change induced by 10 μM peptide was totally abolished by Y-27632, an inhibitor of p160 ROCK which is the downstream signal of G 12/13 pathways. The TFRRR-peptide, YFLLRNP, and the physiological agonist thrombin selectively activated G12/13 pathways at low concentrations and began to activate both Gq and G12/13 pathways with increased concentrations. Similar to SFLLRN, the TFRRRpeptide caused phosphorylation of Akt and Erk in a P2Y 12 receptor-dependent manner, and p-38 MAP kinase activation in a P2Y 12 -independent manner. The effects of this peptide are elicited by the first six amino acids (TFRRRL) whereas the remaining peptide (LSRATR), TFERRN, or TFEERN had no effects on platelets. We conclude that TFRRRL activates human platelets through the PAR-1 receptors.

show abstract

How the protease thrombin talks to cells

Cited by 547 publications

References 65 publications

Endothelial cell functions

Endothelial cell functions

Thrombin Induces Mast Cell Adhesion to Fibronectin: Evidence for Involvement of Protease-Activated Receptor-1

Characterization of a new peptide agonist of the protease-activated receptor-1

Contact Info

Product

Resources

About