6533b850fe1ef96bd12a835e

RESEARCH PRODUCT

Tissue factor at the crossroad of coagulation and cell signaling

Wolfram RufWolfram RufAndrea S. RothmeierH. ZelayaH. Zelaya

subject

0301 basic medicineCell signalingProteasesCIENCIAS MÉDICAS Y DE LA SALUDIntegrinInmunologíaFactor VIIaThromboplastin03 medical and health sciencesTissue factorPROTEINASE- ACTIVATED RECEPTORSNeoplasmsmedicineAnimalsHumansReceptor PAR-2Myeloid CellsHEMOSTASISProtease-activated receptorENDOTHELIAL PROTEIN C RECEPTORBlood CoagulationInflammationEndothelial protein C receptorInnate immune systembiologyChemistryEndothelial CellsThrombosisInflammasomeHematologyCell biologyTHROMBOSISMedicina Básica030104 developmental biologyFactor Xabiology.proteinPROTEIN DISULFIDE-ISOMERASESSignal Transductionmedicine.drug

description

The tissue factor (TF) pathway plays a central role in hemostasis and thrombo-inflammatory diseases. Although structure-function relationships of the TF initiation complex are elucidated, new facets of the dynamic regulation of TF?s activities on cells continue to emerge. Cellular pathways that render TF non-coagulant participate in signaling of distinct TF complexes with associated proteases through the protease-activated receptor (PAR) family of G-protein coupled receptors. Additional coreceptors, including the endothelial protein C receptor (EPCR) and integrins, confer signaling specificity by directing subcellular localization and trafficking. We here review how TF is switchedbetween its role in coagulation and cell signaling through thiol-disulfide exchange reactions in the context of physiologically relevant lipid microdomains. Inflammatory mediators, including reactive oxygen species, activators of the inflammasome, and the complement cascade play pivotal roles inTF procoagulant activation on monocytes, macrophages and endothelial cells. We furthermore discuss how TF, intracellular ligands, co-receptors, and associated proteases are integrated in PARdependent cell signaling pathways controlling innate immunity, cancer, and metabolic inflammation.Knowledge of the precise interactions of TF in coagulation and cell signaling is important for understanding effects of new anticoagulants beyond thrombosis and identification of new applications of these drugs for potential additional therapeutic benefits. Fil: Zelaya, María Hortensia del Rosario. Center For Thrombosis And Hemostasis Mainz (cth); Alemania. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clínica Aplicada; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentina Fil: Rothmeier, Andrea. The Scripps Research Institute; Estados Unidos Fil: Ruf, Wolfram. Center For Thrombosis And Hemostasis Mainz (cth); Alemania. The Scripps Research Institute; Estados Unidos. German Center For Cardiovascular Research (dzhk); Alemania

yearjournalcountryeditionlanguage
2018-10-01Journal of Thrombosis and Haemostasis
https://doi.org/10.1111/jth.14246