The Experts below are selected from a list of 1668 Experts worldwide ranked by ideXlab platform

Michael C. Berndt - One of the best experts on this subject based on the ideXlab platform.

  • Signal Transduction (1930 articles)
    2013
    Co-Authors: Michael C. Berndt, Robert K. Andrews, Adam D Munday, Christina A. Mitchell
    Abstract:

    doi:10.1182/blood.V98.3.681 Interaction of calmodulin with the cytoplasmic domain of the Platelet Membrane Glycoprotein Ib-IX-V comple

  • bruton tyrosine kinase is essential for botrocetin vwf induced signaling and gpib dependent thrombus formation in vivo
    Blood, 2006
    Co-Authors: J Liu, Michael C. Berndt, Carl W. Jackson, Malinda E C Fitzgerald, Kent T Gartner
    Abstract:

    Botrocetin (bt)-facilitated binding of von Willebrand factor (VWF) to the Platelet Membrane Glycoprotein (GP) Ib-IX-V complex on Platelets in suspension initiates a signaling cascade that causes αIIbβ3 activation and Platelet aggregation. Previous work has demonstrated that bt/VWF-mediated agglutination activates αIIbβ3 and elicits ATP secretion in a thromboxane A2 (TxA2)-dependent manner. The signaling that results in TxA2 production was shown to be initiated by Lyn, enhanced by Src, and propagated through Syk, SLP-76, PI3K, PLCγ2, and PKC. Here, we demonstrate that the signaling elicited by GPIb-mediated agglutination that results in TxA2 production is dependent on Bruton tyrosine kinase (Btk). The results demonstrate that Btk is downstream of Lyn, Syk, SLP-76, and PI3K; upstream of ERK1/2, PLCγ2, and PKC; and greatly enhances Akt phosphorylation. The relationship(s), if any, between ERK1/2, PLCγ2, and PKC were not elucidated. The requirement for Btk and TxA2 receptor function in GPIb-dependent arterial thrombosis was confirmed in vivo by characterizing blood flow in ferric chloride-treated mouse carotid arteries. These results demonstrate that the Btk family kinase, Tec, cannot provide the function(s) missing because of the absence of Btk and that Btk is essential for both bt/VWF-mediated agglutination-induced TxA2 production and GPIb-dependent stable arterial thrombus formation in vivo.

  • botrocetin vwf induced signaling through gpib ix v produces txa2 in an αiibβ3 and aggregation independent manner
    Blood, 2005
    Co-Authors: J Liu, Michael C. Berndt, Tamara I. Pestina, Carl W. Jackson
    Abstract:

    Binding of von Willebrand factor (VWF) to the Platelet Membrane Glycoprotein (GP) Ib-IX-V complex initiates a signaling cascade that causes αIIbβ3 activation and Platelet aggregation. Previous work demonstrated that botrocetin (bt)/VWF–mediated agglutination activates αIIbβ3 and elicits adenosine triphosphate (ATP) secretion in a thromboxane A2 (TxA2)– and Ca2+-dependent manner. This agglutination-elicited TxA2 production occurs in the absence of ATP secretion. However, the signaling components and signaling network or pathway activated by GPIb-mediated agglutination to cause TxA2 production have not been identified. Therefore, the focus of this study was to elucidate at least part of the signal transduction network or pathway activated by GPIb-mediated agglutination to cause TxA2 production. The phosphatidylinositol 3-kinase (PI3K) selective inhibitor wortmannin, and mouse Platelets deficient in Lyn, Src, Syk, Src homology 2 (SH2) domain–containing leukocyte protein 76 (SLP-76), phospholipase Cγ2 (PLCγ2), linker for activation of T cells (LAT), or Fc receptor γ-chain (FcRγ-chain) were used for these studies. LAT and FcRγ-chain were found not to be required for agglutination-driven TxA2 production or activation of αIIbβ3, but were required for granule secretion and aggregation. The results also clearly demonstrate that bt/VWF-mediated agglutination-induced TxA2 production is dependent on signaling apparently initiated by Lyn, enhanced by Src, and propagated through Syk, SLP-76, PI3K, PLCγ2, and protein kinase C (PKC).

  • the roles of adp and txa2 in botrocetin vwf induced aggregation of washed Platelets
    Journal of Thrombosis and Haemostasis, 2004
    Co-Authors: J Liu, Michael C. Berndt, Tamara I. Pestina, Shirley A. Steward, Carl W. Jackson, T K Gartner
    Abstract:

    Summary. Background: Binding of von Willebrand factor (VWF) to the Platelet Membrane Glycoprotein (GP) Ib-IX-V complex initiates a cascade of events leading to αIIbβ3 activation and Platelet aggregation. The roles of ADP and thromboxane A2 (TXA2) in agglutination-induced GPIbα-mediated Platelet activation have not been fully described. Methods: Botrocetin and human VWF were used to stimulate washed mouse Platelets. Platelets deficient in TXA2 receptors, Gαq, or αIIbβ3, and inhibitors and chelating agents were used to investigate the roles of TXA2, ADP, αIIbβ3 and Ca2+ in botrocetin/VWF-induced signaling. Results: Our data demonstrate that botrocetin/VWF/GPIbα-mediated agglutination results in calcium-independent protein kinase C (PKC) and phospholipase A2 (PLA2) activities required for GPIbα-elicited TXA2 production that in turn causes dense granule secretion. Aggregation of washed Platelets requires TXA2-induced αIIbβ3 activation and ADP signaling. TXA2 or ADP can activate αIIbβ3, but both are required for α-granule secretion and aggregation. Botrocetin/VWF-induced dense granule secretion is Gαq-dependent. α-Granule secretion requires initial ADP signaling through P2Y1 and subsequent signaling through P2Y12. Signaling initiated by agglutination is propagated and amplified in an αIIbβ3-dependent manner. Conclusions: In contrast to adhesion or shear stress-induced GPIb-elicited signaling, agglutination-elicited GPIb signaling that activates αIIbβ3 requires TXA2. Agglutination-elicited TXA2 production is independent of Ca2+ influx and mobilization of internal Ca2+ stores. Therefore, our results demonstrate that agglutination-elicited GPIb signaling causes αIIbβ3 activation by a mechanism that is distinct from those used by adhesion, or shear stress-induced GPIb signaling.

  • interaction of calmodulin with the cytoplasmic domain of the Platelet Membrane Glycoprotein ib ix v complex
    Blood, 2001
    Co-Authors: Robert K. Andrews, Adam D Munday, Christina Anne Mitchell, Michael C. Berndt
    Abstract:

    Engagement of Platelet Membrane Glycoprotein (GP) Ib-IX-V by von Willebrand factor triggers Ca++-dependent activation of αIIbβ3, resulting in (patho)physiological thrombus formation. It is demonstrated here that the cytoplasmic domain of GPIb-IX-V associates with cytosolic calmodulin. First, an anti-GPIbα antibody coimmunoprecipitated GPIb-IX and calmodulin from Platelet lysates. Following Platelet stimulation, calmodulin dissociated from GPIb-IX and, like the GPIb-IX–associated proteins 14-3-3ζ and p85, redistributed to the activated cytoskeleton. Second, a synthetic peptide based on the cytoplasmic sequence of GPIbβ, R149–L167 (single-letter amino acid codes), affinity-isolated calmodulin from Platelet cytosol in the presence of Ca++ as confirmed by comigration with bovine calmodulin on sodium dodecyl sulfate–polyacrylamide gels, by sequence analysis, and by immunoreactivity with the use of an anticalmodulin antibody. The Membrane-proximal GPIbβ sequence was analogous to a previously reported calmodulin-binding sequence in the leukocyte adhesion receptor, L-selectin. In addition, the cytoplasmic sequence of GPV, K529–G544, was analogous to a calmodulin-binding IQ motif within the α1c subunit of L-type Ca++ channels. Calmodulin coimmunoprecipitated with GPV from resting Platelet lysates, but was dissociated in stimulated Platelets. A GPV-related synthetic peptide also bound calmodulin and induced a Ca++-dependent shift on nondenaturing gels. Together, these results suggest separate regions of GPIb-IX-V can directly bind calmodulin, and this novel interaction potentially regulates aspects of GPIb-IX-V–dependent Platelet activation.

Robert K. Andrews - One of the best experts on this subject based on the ideXlab platform.

  • Signal Transduction (1930 articles)
    2013
    Co-Authors: Michael C. Berndt, Robert K. Andrews, Adam D Munday, Christina A. Mitchell
    Abstract:

    doi:10.1182/blood.V98.3.681 Interaction of calmodulin with the cytoplasmic domain of the Platelet Membrane Glycoprotein Ib-IX-V comple

  • interaction of calmodulin with the cytoplasmic domain of the Platelet Membrane Glycoprotein ib ix v complex
    Blood, 2001
    Co-Authors: Robert K. Andrews, Adam D Munday, Christina Anne Mitchell, Michael C. Berndt
    Abstract:

    Engagement of Platelet Membrane Glycoprotein (GP) Ib-IX-V by von Willebrand factor triggers Ca++-dependent activation of αIIbβ3, resulting in (patho)physiological thrombus formation. It is demonstrated here that the cytoplasmic domain of GPIb-IX-V associates with cytosolic calmodulin. First, an anti-GPIbα antibody coimmunoprecipitated GPIb-IX and calmodulin from Platelet lysates. Following Platelet stimulation, calmodulin dissociated from GPIb-IX and, like the GPIb-IX–associated proteins 14-3-3ζ and p85, redistributed to the activated cytoskeleton. Second, a synthetic peptide based on the cytoplasmic sequence of GPIbβ, R149–L167 (single-letter amino acid codes), affinity-isolated calmodulin from Platelet cytosol in the presence of Ca++ as confirmed by comigration with bovine calmodulin on sodium dodecyl sulfate–polyacrylamide gels, by sequence analysis, and by immunoreactivity with the use of an anticalmodulin antibody. The Membrane-proximal GPIbβ sequence was analogous to a previously reported calmodulin-binding sequence in the leukocyte adhesion receptor, L-selectin. In addition, the cytoplasmic sequence of GPV, K529–G544, was analogous to a calmodulin-binding IQ motif within the α1c subunit of L-type Ca++ channels. Calmodulin coimmunoprecipitated with GPV from resting Platelet lysates, but was dissociated in stimulated Platelets. A GPV-related synthetic peptide also bound calmodulin and induced a Ca++-dependent shift on nondenaturing gels. Together, these results suggest separate regions of GPIb-IX-V can directly bind calmodulin, and this novel interaction potentially regulates aspects of GPIb-IX-V–dependent Platelet activation.

  • a novel viper venom metalloproteinase alborhagin is an agonist at the Platelet collagen receptor gpvi
    Journal of Biological Chemistry, 2001
    Co-Authors: Robert K. Andrews, Michael C. Berndt, Elizabeth E. Gardiner, David Tulasne, Bernhard Nieswandt, Naoki Asazuma, Oscar Berlanga, Ian A Smith, Stephen P Watson
    Abstract:

    Abstract The interaction of Platelet Membrane Glycoprotein VI (GPVI) with collagen can initiate (patho)physiological thrombus formation. The viper venom C-type lectin family proteins convulxin and alboaggregin-A activate Platelets by interacting with GPVI. In this study, we isolated from white-lipped tree viper (Trimeresurus albolabris) venom, alborhagin, which is functionally related to convulxin because it activates Platelets but is structurally different and related to venom metalloproteinases. Alborhagin-induced Platelet aggregation (EC50, <7.5 μg/ml) was inhibitable by an anti-αIIbβ3 antibody, CRC64, and the Src family kinase inhibitor PP1, suggesting that alborhagin activates Platelets, leading to αIIbβ3-dependent aggregation. Additional evidence suggested that, like convulxin, alborhagin activated Platelets by a mechanism involving GPVI. First, alborhagin- and convulxin-treated Platelets showed a similar tyrosine phosphorylation pattern, including a similar level of phospholipase Cγ2 phosphorylation. Second, alborhagin induced GPVI-dependent responses in GPVI-transfected K562 and Jurkat cells. Third, alborhagin-dependent aggregation of mouse Platelets was inhibited by the anti-GPVI monoclonal antibody JAQ1. Alborhagin had minimal effect on convulxin binding to GPVI-expressing cells, indicating that these venom proteins may recognize distinct binding sites. Characterization of alborhagin as a GPVI agonist that is structurally distinct from convulxin demonstrates the versatility of snake venom toxins and provides a novel probe for GPVI-dependent Platelet activation.

  • a novel viper venom metalloproteinase alborhagin is an agonist at the Platelet collagen receptor gpvi
    Journal of Biological Chemistry, 2001
    Co-Authors: Robert K. Andrews, Michael C. Berndt, Elizabeth E. Gardiner, David Tulasne, Bernhard Nieswandt, Naoki Asazuma, Oscar Berlanga, Ian A Smith, Stephen P Watson
    Abstract:

    The interaction of Platelet Membrane Glycoprotein VI (GPVI) with collagen can initiate (patho)physiological thrombus formation. The viper venom C-type lectin family proteins convulxin and alboaggregin-A activate Platelets by interacting with GPVI. In this study, we isolated from white-lipped tree viper (Trimeresurus albolabris) venom, alborhagin, which is functionally related to convulxin because it activates Platelets but is structurally different and related to venom metalloproteinases. Alborhagin-induced Platelet aggregation (EC50,

  • The Vascular Biology of the Glycoprotein Ib-IX-V Complex
    Thrombosis and haemostasis, 2001
    Co-Authors: Michael C. Berndt, Yang Shen, Sacha M. Dopheide, Elizabeth E. Gardiner, Robert K. Andrews
    Abstract:

    It has long been recognized that binding of von Willebrand factor (vWf) by the Platelet Membrane Glycoprotein (GP) Ib-IX-V complex initiates the cascade of events leading to thrombosis and haemostasis. In the last several years, however, it has become apparent that the GP Ib-IX-V complex plays a much broader role in vascular biology, a recognition in part due to the identification of novel adhesive ligands for GP Ib-IX-V such as P-selectin and Mac-1. Binding of vWf by the GP Ib-IX-V complex is also important in formation of the developing thrombus. Platelets can utilize the GP Ib-IX-V complex and PSGL-1 to roll on activated endothelium via surface-expressed endothelial P-selectin. The GP Ib-IX-V complex can bind the I domain of Mac-1, a binding interaction potentially relevant to transmigration of macrophages through mural thrombus, a process required for vessel remodeling post angioplasty. This review will focus on recent advances in our understanding of the structure and function of this important Platelet receptor, with particular emphasis on insights made within the last two years.

Stephen P Watson - One of the best experts on this subject based on the ideXlab platform.

  • a novel viper venom metalloproteinase alborhagin is an agonist at the Platelet collagen receptor gpvi
    Journal of Biological Chemistry, 2001
    Co-Authors: Robert K. Andrews, Michael C. Berndt, Elizabeth E. Gardiner, David Tulasne, Bernhard Nieswandt, Naoki Asazuma, Oscar Berlanga, Ian A Smith, Stephen P Watson
    Abstract:

    Abstract The interaction of Platelet Membrane Glycoprotein VI (GPVI) with collagen can initiate (patho)physiological thrombus formation. The viper venom C-type lectin family proteins convulxin and alboaggregin-A activate Platelets by interacting with GPVI. In this study, we isolated from white-lipped tree viper (Trimeresurus albolabris) venom, alborhagin, which is functionally related to convulxin because it activates Platelets but is structurally different and related to venom metalloproteinases. Alborhagin-induced Platelet aggregation (EC50, <7.5 μg/ml) was inhibitable by an anti-αIIbβ3 antibody, CRC64, and the Src family kinase inhibitor PP1, suggesting that alborhagin activates Platelets, leading to αIIbβ3-dependent aggregation. Additional evidence suggested that, like convulxin, alborhagin activated Platelets by a mechanism involving GPVI. First, alborhagin- and convulxin-treated Platelets showed a similar tyrosine phosphorylation pattern, including a similar level of phospholipase Cγ2 phosphorylation. Second, alborhagin induced GPVI-dependent responses in GPVI-transfected K562 and Jurkat cells. Third, alborhagin-dependent aggregation of mouse Platelets was inhibited by the anti-GPVI monoclonal antibody JAQ1. Alborhagin had minimal effect on convulxin binding to GPVI-expressing cells, indicating that these venom proteins may recognize distinct binding sites. Characterization of alborhagin as a GPVI agonist that is structurally distinct from convulxin demonstrates the versatility of snake venom toxins and provides a novel probe for GPVI-dependent Platelet activation.

  • a novel viper venom metalloproteinase alborhagin is an agonist at the Platelet collagen receptor gpvi
    Journal of Biological Chemistry, 2001
    Co-Authors: Robert K. Andrews, Michael C. Berndt, Elizabeth E. Gardiner, David Tulasne, Bernhard Nieswandt, Naoki Asazuma, Oscar Berlanga, Ian A Smith, Stephen P Watson
    Abstract:

    The interaction of Platelet Membrane Glycoprotein VI (GPVI) with collagen can initiate (patho)physiological thrombus formation. The viper venom C-type lectin family proteins convulxin and alboaggregin-A activate Platelets by interacting with GPVI. In this study, we isolated from white-lipped tree viper (Trimeresurus albolabris) venom, alborhagin, which is functionally related to convulxin because it activates Platelets but is structurally different and related to venom metalloproteinases. Alborhagin-induced Platelet aggregation (EC50,

Elizabeth E. Gardiner - One of the best experts on this subject based on the ideXlab platform.

  • a novel viper venom metalloproteinase alborhagin is an agonist at the Platelet collagen receptor gpvi
    Journal of Biological Chemistry, 2001
    Co-Authors: Robert K. Andrews, Michael C. Berndt, Elizabeth E. Gardiner, David Tulasne, Bernhard Nieswandt, Naoki Asazuma, Oscar Berlanga, Ian A Smith, Stephen P Watson
    Abstract:

    The interaction of Platelet Membrane Glycoprotein VI (GPVI) with collagen can initiate (patho)physiological thrombus formation. The viper venom C-type lectin family proteins convulxin and alboaggregin-A activate Platelets by interacting with GPVI. In this study, we isolated from white-lipped tree viper (Trimeresurus albolabris) venom, alborhagin, which is functionally related to convulxin because it activates Platelets but is structurally different and related to venom metalloproteinases. Alborhagin-induced Platelet aggregation (EC50,

  • a novel viper venom metalloproteinase alborhagin is an agonist at the Platelet collagen receptor gpvi
    Journal of Biological Chemistry, 2001
    Co-Authors: Robert K. Andrews, Michael C. Berndt, Elizabeth E. Gardiner, David Tulasne, Bernhard Nieswandt, Naoki Asazuma, Oscar Berlanga, Ian A Smith, Stephen P Watson
    Abstract:

    Abstract The interaction of Platelet Membrane Glycoprotein VI (GPVI) with collagen can initiate (patho)physiological thrombus formation. The viper venom C-type lectin family proteins convulxin and alboaggregin-A activate Platelets by interacting with GPVI. In this study, we isolated from white-lipped tree viper (Trimeresurus albolabris) venom, alborhagin, which is functionally related to convulxin because it activates Platelets but is structurally different and related to venom metalloproteinases. Alborhagin-induced Platelet aggregation (EC50, <7.5 μg/ml) was inhibitable by an anti-αIIbβ3 antibody, CRC64, and the Src family kinase inhibitor PP1, suggesting that alborhagin activates Platelets, leading to αIIbβ3-dependent aggregation. Additional evidence suggested that, like convulxin, alborhagin activated Platelets by a mechanism involving GPVI. First, alborhagin- and convulxin-treated Platelets showed a similar tyrosine phosphorylation pattern, including a similar level of phospholipase Cγ2 phosphorylation. Second, alborhagin induced GPVI-dependent responses in GPVI-transfected K562 and Jurkat cells. Third, alborhagin-dependent aggregation of mouse Platelets was inhibited by the anti-GPVI monoclonal antibody JAQ1. Alborhagin had minimal effect on convulxin binding to GPVI-expressing cells, indicating that these venom proteins may recognize distinct binding sites. Characterization of alborhagin as a GPVI agonist that is structurally distinct from convulxin demonstrates the versatility of snake venom toxins and provides a novel probe for GPVI-dependent Platelet activation.

  • The Vascular Biology of the Glycoprotein Ib-IX-V Complex
    Thrombosis and haemostasis, 2001
    Co-Authors: Michael C. Berndt, Yang Shen, Sacha M. Dopheide, Elizabeth E. Gardiner, Robert K. Andrews
    Abstract:

    It has long been recognized that binding of von Willebrand factor (vWf) by the Platelet Membrane Glycoprotein (GP) Ib-IX-V complex initiates the cascade of events leading to thrombosis and haemostasis. In the last several years, however, it has become apparent that the GP Ib-IX-V complex plays a much broader role in vascular biology, a recognition in part due to the identification of novel adhesive ligands for GP Ib-IX-V such as P-selectin and Mac-1. Binding of vWf by the GP Ib-IX-V complex is also important in formation of the developing thrombus. Platelets can utilize the GP Ib-IX-V complex and PSGL-1 to roll on activated endothelium via surface-expressed endothelial P-selectin. The GP Ib-IX-V complex can bind the I domain of Mac-1, a binding interaction potentially relevant to transmigration of macrophages through mural thrombus, a process required for vessel remodeling post angioplasty. This review will focus on recent advances in our understanding of the structure and function of this important Platelet receptor, with particular emphasis on insights made within the last two years.

Paul M Sullam - One of the best experts on this subject based on the ideXlab platform.