0000000000394705

AUTHOR

Sagarika Chakrabarty

showing 4 related works from this author

Identification of the integrin-binding site on coagulation factor VIIa required for proangiogenic PAR2 signaling.

2018

The tissue factor (TF) pathway serves both hemostasis and cell signaling, but how cells control these divergent functions of TF remains incompletely understood. TF is the receptor and scaffold of coagulation proteases cleaving protease-activated receptor 2 (PAR2) that plays pivotal roles in angiogenesis and tumor development. Here we demonstrate that coagulation factor VIIa (FVIIa) elicits TF cytoplasmic domain-dependent proangiogenic cell signaling independent of the alternative PAR2 activator matriptase. We identify a Lys-Gly-Glu (KGE) integrin-binding motif in the FVIIa protease domain that is required for association of the TF-FVIIa complex with the active conformer of integrin β1. A po…

0301 basic medicineCell signalingImmunologyIntegrinNeovascularization PhysiologicFactor VIIa030204 cardiovascular system & hematologyBiochemistryThromboplastinThrombosis and Hemostasis03 medical and health sciencesTissue factorMice0302 clinical medicineAnimalsHumansReceptor PAR-2Protein Interaction Domains and MotifsProtein Interaction MapsProtein kinase ACells CulturedIntegrin bindingBinding SitesbiologyChemistryIntegrin beta1Cell BiologyHematologyCell biologyCrosstalk (biology)030104 developmental biologyADP-Ribosylation Factor 6biology.proteinNIH 3T3 CellsPhosphorylationSignal transductionProtein BindingSignal TransductionBlood
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EPCR/PAR1 Signaling Navigates Long-Term Repopulating Hematopoietic Stem Cell Bone Marrow Homing to Thrombomodulin-Enriched Blood Vessels

2015

Abstract Bone marrow (BM) homing and lodgment of long-term repopulating hematopoietic stem cells (LT-HSCs) is an active and essential first step in clinical stem cell transplantation. EPCR is expressed by murine BM LT-HSCs endowed with the highest repopulation potential and its ligand, activated protein C (aPC), has anticoagulant and anti-sepsis effects in EPCR+/PAR1+ endothelial cells. We recently found that signaling cascades, traditionally viewed as coagulation and inflammation related, also independently control EPCR+ LT-HSC BM retention and recruitment to the blood via distinct PAR1 mediated pathways. EPCR/PAR1 signaling retains LT-HSCs in the BM by restricting nitric oxide (NO) produc…

ImmunologyHematopoietic stem cellCell BiologyHematologyBiologyBiochemistryCell biologyTransplantationEndothelial stem cellHaematopoiesismedicine.anatomical_structureCdc42 GTP-Binding ProteinImmunologymedicineStem cellProgenitor cellHoming (hematopoietic)Blood
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PAR1 signaling regulates the retention and recruitment of EPCR-expressing bone marrow hematopoietic stem cells

2015

Retention of long-term repopulating hematopoietic stem cells (LT-HSCs) in the bone marrow is essential for hematopoiesis and for protection from myelotoxic injury. We report that signaling cascades that are traditionally viewed as coagulation related also control retention of endothelial protein C receptor-positive (EPCR(+)) LT-HSCs in the bone marrow and their recruitment to the blood via two pathways mediated by protease activated receptor 1 (PAR1). Thrombin-PAR1 signaling induces nitric oxide (NO) production, leading to EPCR shedding mediated by tumor necrosis factor-α-converting enzyme (TACE), enhanced CXCL12-CXCR4-induced motility and rapid stem and progenitor cell mobilization. Conver…

Receptors CXCR4Receptors Cell SurfaceADAM17 ProteinIntegrin alpha4beta1BiologyNitric OxideArticleGeneral Biochemistry Genetics and Molecular BiologyMiceBone MarrowCell MovementCell AdhesionmedicineAnimalsReceptor PAR-1Progenitor cellcdc42 GTP-Binding ProteinCell adhesionEndothelial protein C receptorThrombinEndothelial Protein C ReceptorGeneral MedicineHematopoietic Stem CellsChemokine CXCL12Cell biologyMice Inbred C57BLTransplantationADAM ProteinsHaematopoiesismedicine.anatomical_structureCdc42 GTP-Binding ProteinImmunologyBone marrowStem cellProtein CSignal TransductionNature Medicine
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Inverse PAR1 Activity of Hematopoietic Stem Cells and BM Stromal Cells Mediates G-CSF-Induced Mobilization By Regulation of Nitric Oxide Generation

2016

Abstract Hematopoietic stem and progenitor cell (HSPC) egress from the bone marrow (BM) to the circulation is tightly regulated and is accelerated during stress conditions, a process utilized for BM harvest. Recently, we demonstrated that mouse long term repopulating hematopoietic stem cell (LT-HSC) BM retention and their rapid release to the blood circulation are governed by a switch in nitric oxide (NO) generation via distinct coagulation-related protease activated receptor 1 (PAR1) cascades (Gur-Cohen S. et al., NM, 2016). Herein we report that surface PAR1 expression can be exploited and serve as a positive predictive marker for the efficiency of human CD34+ HSPC mobilization among heal…

0301 basic medicineStromal cellbiologyChemistryImmunologyMesenchymal stem cellHematopoietic stem cellCell BiologyHematologyBiochemistryCell biology03 medical and health sciencesHaematopoiesis030104 developmental biologymedicine.anatomical_structuremedicinebiology.proteinStromal cell-derived factor 1Progenitor cellStem cellHematopoietic Stem Cell MobilizationBlood
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