@article{ReinhardHalbrueggeScheeretal.1992,
  author    = {Reinhard, Matthias and Halbr{\"u}gge, Maria and Scheer, Ulrich and Wiegand, Christiane and Jockusch, Brigitte M. and Walter, Ulrich},
  title     = {The 46/50 kDa phosphoprotein VASP purified from human platelets is a novel protein associated with actin filaments and focal contacts},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-34246},
  year      = {1992},
  abstract  = {Vasoactive agents which elevate either cGMP or cAMP inhibit platelet activation by pathways sharing at least one component, the 46/50 kDa vasodilator-stimulated phosphoprotein (V ASP). V ASP is stoichiometrically phosphorylated by both cGMP-dependent and cAMPdependent protein kinases in intact human platelets, and its phosphorylation correlates very well with platelet inhibition caused by cGMP- and cAMP-elevating agents. Here we report that in human platelets spread on glass, V ASP is associated predominantly with the distal parts of radial micro filament bundles and with microfilaments outlining the periphery, whereas less V ASP is associated with a central microfilamentous ring. V ASP is also detectable in a variety of different cell types including fibroblasts and epithelial cells. In fibroblasts, V ASP is concentrated at focal contact areas, along microfilament bundles (stress fibres) in a punctate pattern, in the periphery of protruding lamellae, and is phosphorylated by cGMP- and cAMP-dependent protein kinases in response to appropriate stimuli. Evidence for the direct binding of V ASP to F -actin is also presented. The data demonstrate that V ASP is a novel phosphoprotein associated with actin filaments and focal contact areas, i.e. transmembrane junctions between microfilaments and the extracellular matrix.},
  language  = {de}
}
@article{NavdaevSubramanianPetuninetal.2014,
  author    = {Navdaev, Alexey and Subramanian, Hariharan and Petunin, Alexey and Clemetson, Kenneth J. and Gambaryan, Stepan and Walter, Ulrich},
  title     = {Echicetin Coated Polystyrene Beads: A Novel Tool to Investigate GPIb-Specific Platelet Activation and Aggregation},
  series = {PLoS ONE},
  volume    = {9},
  journal   = {PLoS ONE},
  number    = {4},
  issn      = {1932-6203},
  doi       = {10.1371/journal.pone.0093569},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119815},
  pages     = {e93569},
  year      = {2014},
  abstract  = {von Willebrand factor/ristocetin (vWF/R) induces GPIb-dependent platelet agglutination and activation of αIIbβ3 integrin, which also binds vWF. These conditions make it difficult to investigate GPIb-specific signaling pathways in washed platelets. Here, we investigated the specific mechanisms of GPIb signaling using echicetin-coated polystyrene beads, which specifically activate GPIb. We compared platelet activation induced by echicetin beads to vWF/R. Human platelets were stimulated with polystyrene beads coated with increasing amounts of echicetin and platelet activation by echicetin beads was then investigated to reveal GPIb specific signaling. Echicetin beads induced αIIbβ3-dependent aggregation of washed platelets, while under the same conditions vWF/R treatment led only to αIIbβ3-independent platelet agglutination. The average distance between the echicetin molecules on the polystyrene beads must be less than 7 nm for full platelet activation, while the total amount of echicetin used for activation is not critical. Echicetin beads induced strong phosphorylation of several proteins including p38, ERK and PKB. Synergistic signaling via P2Y12 and thromboxane receptor through secreted ADP and TxA2, respectively, were important for echicetin bead triggered platelet activation. Activation of PKG by the NO/sGC/cGMP pathway inhibited echicetin bead-induced platelet aggregation. Echicetin-coated beads are powerful and reliable tools to study signaling in human platelets activated solely via GPIb and GPIb-triggered pathways.},
  language  = {en}
}
@article{KraftBenzAustinatetal.2010,
  author    = {Kraft, Peter and Benz, Peter Michael and Austinat, Madeleine and Brede, Marc Elmar and Schuh, Kai and Walter, Ulrich and Stoll, Guido and Kleinschnitz, Christoph},
  title     = {Deficiency of Vasodilator-Stimulated Phosphoprotein (VASP) Increases Blood-Brain-Barrier Damage and Edema Formation after Ischemic Stroke in Mice},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68522},
  year      = {2010},
  abstract  = {Background: Stroke-induced brain edema formation is a frequent cause of secondary infarct growth and deterioration of neurological function. The molecular mechanisms underlying edema formation after stroke are largely unknown. Vasodilator-stimulated phosphoprotein (VASP) is an important regulator of actin dynamics and stabilizes endothelial barriers through interaction with cell-cell contacts and focal adhesion sites. Hypoxia has been shown to foster vascular leakage by downregulation of VASP in vitro but the significance of VASP for regulating vascular permeability in the hypoxic brain in vivo awaits clarification. Methodology/Principal Findings: Focal cerebral ischemia was induced in Vasp2/2 mice and wild-type (WT) littermates by transient middle cerebral artery occlusion (tMCAO). Evan's Blue tracer was applied to visualize the extent of blood-brainbarrier (BBB) damage. Brain edema formation and infarct volumes were calculated from 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain slices. Both mouse groups were carefully controlled for anatomical and physiological parameters relevant for edema formation and stroke outcome. BBB damage (p,0.05) and edema volumes (1.7 mm360.5 mm3 versus 0.8 mm360.4 mm3; p,0.0001) were significantly enhanced in Vasp2/2 mice compared to controls on day 1 after tMCAO. This was accompanied by a significant increase in infarct size (56.1 mm3617.3 mm3 versus 39.3 mm3610.7 mm3, respectively; p,0.01) and a non significant trend (p.0.05) towards worse neurological outcomes. Conclusion: Our study identifies VASP as critical regulator of BBB maintenance during acute ischemic stroke. Therapeutic modulation of VASP or VASP-dependent signalling pathways could become a novel strategy to combat excessive edema formation in ischemic brain damage.},
  subject      = {Vasodilatator-stimuliertes Phosphoprotein},
  language  = {en}
}
@article{GambaryanSubramanianKehreretal.2016,
  author    = {Gambaryan, Stepan and Subramanian, Hariharan and Kehrer, Linda and Mindukshev, Igor and Sudnitsyna, Julia and Reiss, Cora and Rukoyatkina, Natalia and Friebe, Andreas and Sharina, Iraida and Martin, Emil and Walter, Ulrich},
  title     = {Erythrocytes do not activate purified and platelet soluble guanylate cyclases even in conditions favourable for NO synthesis},
  series = {Cell Communication and Signaling},
  volume    = {14},
  journal   = {Cell Communication and Signaling},
  number    = {16},
  doi       = {10.1186/s12964-016-0139-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161223},
  year      = {2016},
  abstract  = {Background Direct interaction between Red blood cells (RBCs) and platelets is known for a long time. The bleeding time is prolonged in anemic patients independent of their platelet count and could be corrected by transfusion of RBCs, which indicates that RBCs play an important role in hemostasis and platelet activation. However, in the last few years, opposing mechanisms of platelet inhibition by RBCs derived nitric oxide (NO) were proposed. The aim of our study was to identify whether RBCs could produce NO and activate soluble guanylate cyclase (sGC) in platelets. Methods To test whether RBCs could activate sGC under different conditions (whole blood, under hypoxia, or even loaded with NO), we used our well-established and highly sensitive models of NO-dependent sGC activation in platelets and activation of purified sGC. The activation of sGC was monitored by detecting the phosphorylation of Vasodilator Stimulated Phosphoprotein (VASPS239) by flow cytometry and Western blot. ANOVA followed by Bonferroni's test and Student's t-test were used as appropriate. Results We show that in the whole blood, RBCs prevent NO-mediated inhibition of ADP and TRAP6-induced platelet activation. Likewise, coincubation of RBCs with platelets results in strong inhibition of NO-induced sGC activation. Under hypoxic conditions, incubation of RBCs with NO donor leads to Hb-NO formation which inhibits sGC activation in platelets. Similarly, RBCs inhibit activation of purified sGC, even under conditions optimal for RBC-mediated generation of NO from nitrite. Conclusions All our experiments demonstrate that RBCs act as strong NO scavengers and prevent NO-mediated inhibition of activated platelets. In all tested conditions, RBCs were not able to activate platelet or purified sGC.},
  language  = {en}
}