... work, we have shown that β2GpI selectively inhibits the procoagulant functions of human α-thrombin (αT; i.e. prolongs fibrin clotting time, t c , and inhibits αT-induced platelet aggregation) without affecting the unique anticoagulant activity of the protease, i.e. the proteolytic generation...

...Ilaria Canobbio; Lina Cipolla; Gianni F. Guidetti; Daria Manganaro; Caterina Visconte; Soochong Kim; Mitsuhiko Okigaki; Marco Falasca; Satya P. Kunapuli; Mauro Torti In blood platelets, stimulation of G protein-coupled receptors (GPCRs) by thrombin triggers the activation of Src family kinases...

... coagulation, commonly thought to be due to insufficient functioning of anticoagulation pathways. A small amount of fXa (Factor Xa) produced by Factor VIIa and exposed tissue factor is key to initiating blood coagulation by producing enough thrombin to induce the later stages of coagulation. fXa must bind...

... in the STIM1 (stromal interaction molecule 1)–Orai1 association, as well as in the TRPC1–IP 3 RII (type II IP 3 receptor) interaction, which might be of relevance in platelet function. Treatment of human platelets with thapsigargin or thrombin results in a Ca 2+ -independent association of Homer1 with TRPC1...

.... In the present paper, we report that thrombin mediates shedding of an N-terminal TEM5 fragment of 60 kDa (termed N60) containing the RGD motif in an open conformation. Thrombin directly cleaved rsTEM5 (recombinant soluble TEM5) 5 and 34 residues downstream of the RGD motif, resulting in formation of N60 and its...

...-LOX also generated the 14-HDOHE isomer from DHA. Pharmacological studies using inhibitors and recombinant platelet 12-LOX indicate that they form via esterification of newly formed non-esterified HDOHE. HDOHE-PEs formed at significant rates (2–4 ng/4×10 7 cells) within 2–180 min of thrombin...

...-hTRPC6 antibody, directed towards the C-terminal region, reduces CCE induced by TPEN [ N , N , N ′, N ′-tetrakis-(2-pyridylmethyl)-ethylenediamine], which reduces the intraluminal free Ca 2+ concentration. Cell stimulation with thrombin or extensive Ca 2+ -store depletion by TG (thapsigargin)+ionomycin...

...Kellie J. Hall; Matthew L. Jones; Alastair W. Poole PKC (protein kinase C)δ plays a complex role in platelets, having effects on both positive and negative signalling functions. It is phosphorylated on tyrosine residues in response to thrombin and collagen, and it has recently been shown that Tyr...

...Isaac Jardin; Nidhal Ben Amor; Ahgleb Bartegi; José A. Pariente; Ginés M. Salido; Juan A. Rosado Physiological agonists increase cytosolic free Ca 2+ concentration to regulate a number of cellular processes. The platelet thrombin receptors, PAR (protease-activated receptor) 1 PAR-4 and GPIb-IX-V...

..., in a manner blocked by the PKC inhibitor BIM I (bisindolylmaleimide I). In response to thrombin, VASP was also phosphorylated on Ser 157 , but this response was only partially inhibited by BIM I, indicating PKC-dependent and -independent pathways to VASP phosphorylation by thrombin. Using inhibitors, we have...

... mechanistic interpretations. Such a controversy has arisen over thrombin's conformational response to Na + co-ordination, and in this issue of Biochemical Journal , De Filippis and colleagues put the two structural models of thrombin allostery to the test by returning to the techniques of solution...

...Vincenzo De Filippis; Elisa De Dea; Filippo Lucatello; Roberta Frasson In the present work, the effect of Na + binding on the conformational, stability and molecular recognition properties of thrombin was investigated. The binding of Na + reduces the CD signal in the far-UV region, while increasing...

... and reduced that evoked by thrombin. In contrast, GPN did not modify Ca 2+ mobilization stimulated by ADP or AVP ([arginine]vasopressin). Treatment with nigericin, a proton carrier, and bafilomycin A1, an inhibitor of the vacuolar H + -ATPase, to dissipate the proton gradient into acidic organelles induces...

... stimulation to elucidate receptor-mediated pathways that functionally regulate PLC∊. We demonstrate that EGF (epidermal growth factor), a receptor tyrosine kinase agonist, and LPA (lysophosphatidic acid), S1P (sphingosine 1-phosphate) and thrombin, GPCR (G-protein-coupled receptor) agonists, stimulate PLC...

...Claire J. CHALMERS; Kathryn BALMANNO; Kathryn HADFIELD; Rebecca LEY; Simon J. COOK To investigate the role of thrombin in regulating apoptosis, we have used CCl39 cells, a fibroblast cell line in which thrombin-induced cell proliferation has been extensively studied. Withdrawal of serum from CCl39...

...R. De CRISTOFARO; V. De FILIPPIS Activation of factor VIII (FVIII) by thrombin plays a fundamental role in the amplification of the coagulation cascade and takes place through specific proteolytic cleavages at Arg 372 , Arg 740 and Arg 1689 . Full FVIII activation requires cleavage at Arg 372...

...-BB) and thrombin, the receptor tyrosine kinase (RTK) and G-protein-coupled receptor (GPCR) agonists, respectively. NFATc1 but not NFATc2 or NFATc3 was translocated from the cytoplasm to the nucleus upon treatment of VSMCs with PDGF-BB or thrombin. Translocation of NFATc1 was followed by an increase...

... aggregation, and this induces subsequent outside-in signalling, which enhances platelet activation. Here we studied the involvement of Cbl during αIIb-β3-integrin-mediated signal transduction. During thrombin-induced platelet activation, Cbl was tyrosine phosphorylated, and phosphoinositide 3-kinase (PI 3...

... activation is distinct from that of FAK. In the present study we investigated the mode of Pyk2 activation in human platelets. When platelets were stimulated with thrombin, Pyk2, as well as FAK, was markedly tyrosine-phosphorylated, in a manner mostly dependent on αIIbβ3 integrin-mediated aggregation...

... that fractionates with platelet α-granules, may be involved in linking these processes. We found that Rab6 contains two PKC consensus phosphorylation sites that are evolutionarily conserved. In platelets metabolically labelled with [ 32 P]P i , Rab6 phosphorylation was induced by phorbol esters or by thrombin...

...Marianne J. RATCLIFFE; Caroline SMALES; James M. STADDON Inflammatory mediators such as histamine and thrombin increase the tight-junction permeability of endothelial cells. Tight-junction permeability may be independently controlled, but is dependent on the adherens junction, where adhesion...