DOI: 10.1182/blood-2002-02-0514. Sequential cytoplasmic calcium signals in a 2-stage platelet activation process induced by the glycoprotein Ibα mechanoreceptor

Sequential cytoplasmic calcium signals in a 2-stage platelet activation process induced by the glycoprotein Ibα mechanoreceptor

10.1182/blood-2002-02-0514

Crossref journal-article

American Society of Hematology

Blood (234)

Abstract

We found that the interaction of platelets with immobilized von Willebrand factor (VWF) under flow induces distinct elevations of cytosolic Ca++ concentration ([Ca++]i) that are associated with sequential stages of integrin αIIbβ3 activation. Fluid-dynamic conditions that are compatible with the existence of tensile stress on the bonds between glycoprotein Ibα (GPIbα) and the VWF A1 domain led to Ca++ release from intracellular stores (type α/β peaks), which preceded stationary platelet adhesion. Raised levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate, as well as membrane-permeable calcium chelators, inhibited these [Ca++]ioscillations and prevented stable adhesion without affecting the dynamic characteristics of the typical platelet translocation on VWF mediated by GPIbα. Once adhesion was established through the integrin αIIbβ3, new [Ca++]i oscillations (type γ) of greater amplitude and duration, and involving a transmembrane ion flux, developed in association with the recruitment of additional platelets into aggregates. Degradation of released adenosine diphosphate (ADP) to AMP or inhibition of phosphatidylinositol 3-kinase (PI3-K) prevented this response without affecting stationary adhesion and blocked aggregation. These findings indicate that an initial signal induced by stressed GPIbα-VWF bonds leads to αIIbβ3 activation sufficient to support localized platelet adhesion. Then, additional signals from ADP receptors and possibly ligand-occupied αIIbβ3, with the contribution of a pathway involving PI3-K, amplify platelet activation to the level required for aggregation. Our conclusions modify those proposed by others regarding the mechanisms that regulate signaling between GPIbα and αIIbβ3 and lead to platelet adhesion and aggregation on immobilized VWF.

Bibliography

Mazzucato, M., Pradella, P., Cozzi, M. R., De Marco, L., & Ruggeri, Z. M. (2002). Sequential cytoplasmic calcium signals in a 2-stage platelet activation process induced by the glycoprotein IbÎ± mechanoreceptor. Blood, 100(8), 2793â2800.

Authors 5

Mario Mazzucato (first)
Paola Pradella (additional)
Maria Rita Cozzi (additional)
Luigi De Marco (additional)
Zaverio M. Ruggeri (additional)

References 40 Referenced 147

{'key': '2019111821325920300_B1', 'first-page': '1', 'article-title': 'Platelets, hemostasis and thrombosis.', 'volume-title': 'Von Willebrand Factor and the Mechanisms of Platelet Function.', 'author': 'Ruggeri', 'year': '1998'} / Von Willebrand Factor and the Mechanisms of Platelet Function. / Platelets, hemostasis and thrombosis. by Ruggeri (1998)
10.1056/NEJM199201233260406 / N Engl J Med. / The pathogenesis of coronary artery disease and the acute coronary syndromes (1). by Fuster (1992)
10.1056/NEJM199201303260506 / N Engl J Med. / The pathogenesis of coronary artery disease and the acute coronary syndromes (2). by Fuster (1992)
10.1016/S0092-8674(00)81607-4 / Cell. / Specific synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow. by Savage (1998)
10.1016/S0092-8674(00)80983-6 / Cell. / Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor. by Savage (1996)
10.1182/blood.V94.1.172.413k17_172_178 / Blood. / Contribution of distinct adhesive interactions to platelet aggregation in flowing blood. by Ruggeri (1999)
10.1073/pnas.82.21.7424 / Proc Natl Acad Sci U S A. / Interaction of purified IIB von Willebrand factor with the platelet membrane glycoprotein Ib induces fibrinogen binding to the glycoprotein IIb/IIIa complex and initiates aggregation. by De Marco (1985)
10.1172/JCI113095 / J Clin Invest. / Type IIB von Willebrand factor with normal sialic acid content induces platelet aggregation in the absence of ristocetin: role of platelet activation, fibrinogen, and two distinct membrane receptors. by De Marco (1987)
10.1182/blood.V80.1.113.113 / Blood. / Shear stress-induced von Willebrand factor binding to platelet glycoprotein Ib initiates calcium influx associated with aggregation. by Chow (1992)
10.1055/s-0038-1651640 / Thromb Haemost. / Transmembrane calcium influx associated with von Willebrand factor binding to GP Ib in the initiation of shear-induced platelet aggregation. by Ikeda (1993)
10.1182/blood.V94.4.1149 / Blood. / Cytosolic calcium changes in a process of platelet adhesion and cohesion on a von Willebrand factor-coated surface under flow conditions. by Kuwahara (1999)
10.1074/jbc.M005590200 / J Biol Chem. / Synergistic adhesive interactions and signaling mechanisms operating between platelet glycoprotein Ib/IX and integrin αIIbβ3: studies in human platelets and transfected Chinese hamster ovary cells. by Yap (2000)
10.1074/jbc.M110070200 / J Biol Chem. / Distinct glycoprotein Ib/V/IX and integrin αIIbβ3-dependent calcium signals cooperatively regulate platelet adhesion under flow. by Nesbitt (2002)
10.1016/0092-8674(91)90393-D / Cell. / Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. by Lawrence (1991)
10.1182/blood.V99.1.151 / Blood. / Essential role for phosphoinositide 3-kinase in shear-dependent signaling between platelet glycoprotein Ib/V/IX and integrin αIIbβ3. by Yap (2002)
10.1042/bj2690513 / Biochem J. / Use of fluo-3 to measure cytosolic Ca2+ in platelets and neutrophils: loading cells with the dye, calibration of traces, measurements in the presence of plasma, and buffering of cytosolic Ca2+. by Merritt (1990)
10.1074/jbc.274.10.6586 / J Biol Chem. / Distinct structural attributes regulating von Willebrand factor A1 domain interaction with platelet glycoprotein Ibα under flow. by Miyata (1999)
10.1016/S0021-9258(18)67128-5 / J Biol Chem. / The von Willebrand factor-binding domain of platelet membrane glycoprotein Ib: characterization by monoclonal antibodies and partial amino acid sequence analysis of proteolytic fragments. by Handa (1986)
10.1182/blood.V70.2.475.475 / Blood. / Increased surface expression of the membrane glycoprotein IIb/IIIa complex induced by platelet activation: relationship to the binding of fibrinogen and platelet aggregation. by Niiya (1987)
10.1055/s-0037-1615861 / Thromb Haemost. / Cyclic nucleotides and phosphodiesterases in platelets. by Haslam (1999)
10.1016/S1367-5931(98)80123-3 / Curr Opin Chem Biol. / Chemotherapeutic potential of phosphodiesterase inhibitors. by Perry (1998)
10.1007/BF02285104 / Eur J Clin Pharmacol. / Correlation between theophylline concentration in plasma, erythrocytes and cantharides induces blister fluid and peak expiratory flow in asthma patients. by Philip-Joet (1992)
10.1074/jbc.274.5.3033 / J Biol Chem. / Identification of domains responsible for von Willebrand factor type VI collagen interaction mediating platelet adhesion under high flow. by Mazzucato (1999)
10.1016/S0021-9258(19)37004-8 / J Biol Chem. / Identification of a region in the cytoplasmic domain of the platelet membrane glycoprotein Ib-IX complex that binds to purified actin-binding protein. by Andrews (1992)
10.1074/jbc.271.19.11581 / J Biol Chem. / The cytoplasmic domain of the α-subunit of glycoprotein (GP) Ib mediates attachment of the entire GP Ib-IX complex to the cytoskeleton and regulates von Willebrand factor-induced changes in cell morphology. by Cunningham (1996)
10.1074/jbc.271.13.7362 / J Biol Chem. / Identification of a binding sequence for the 14-3-3 protein within the cytoplasmic domain of the adhesion receptor, platelet glycoprotein Ibα. by Du (1996)
10.1146/annurev.pharmtox.40.1.617 / Annu Rev Pharmacol Toxicol. / 14-3-3 proteins: structure, function, and regulation. by Fu (2000)
10.1074/jbc.275.22.16779 / J Biol Chem. / Signaling across the platelet adhesion receptor glycoprotein Ib-IX induces αIIbβ3 activation both in platelets and a transfected Chinese hamster ovary cell system. by Zaffran (2000)
10.1038/361315a0 / Nature. / Inositol triphosphate and calcium signalling. by Berridge (1993)
10.1016/0006-291X(90)91271-S / Biochem Biophys Res Commun. / Shear stress increases inositol trisphosphate levels in human endothelial cells. by Nollert (1990)
10.1159/000158963 / J Vasc Res. / Fluid shear stress stimulates membrane phospholipid metabolism in cultured human endothelial cells. by Bhagyalakshmi (1992)
10.1152/ajpcell.2000.278.5.C989 / Am J Physiol Cell Physiol. / Ca2+ regulates fluid shear-induced cytoskeletal reorganization and gene expression in osteoblasts. by Chen (2000)
10.1182/blood.V71.5.1366.bloodjournal7151366 / Blood. / Shear-induced platelet aggregation can be mediated by vWF released from platelets, as well as by exogenous large or unusually large vWF multimers, requires adenosine diphosphate, and is resistant to aspirin. by Moake (1988)
10.1182/blood.V98.12.3340 / Blood. / Blockade of adenosine diphosphate receptors P2Y12 and P2Y1 is required to inhibit platelet aggregation in whole blood under flow. by Turner (2001)
10.1016/S0021-9258(18)47130-X / J Biol Chem. / Adhesion receptor activation of phosphatidylinositol 3-kinase: von Willebrand factor stimulates the cytoskeletal association and activation of phosphatidylinositol 3-kinase and pp60c-src in human platelets. by Jackson (1994)
{'key': '2019111821325920300_B36', 'first-page': '15', 'article-title': 'Platelet activation by ADP: the role of ADP antagonists.', 'volume': '32(suppl 1)', 'author': 'Gachet', 'year': '2000', 'journal-title': 'Ann Med.'} / Ann Med. / Platelet activation by ADP: the role of ADP antagonists. by Gachet (2000)
10.1016/S0021-9258(18)89543-6 / J Biol Chem. / Ca2+ transport across the platelet plasma membrane: a role for membrane glycoproteins IIb and IIIa. by Brass (1985)
10.1074/jbc.275.13.9110 / J Biol Chem. / Phosphoinositides are required for store-mediated calcium entry in human platelets. by Rosado (2000)
10.1016/0014-5793(96)00130-5 / FEBS Lett. / Wortmannin inhibits store-mediated calcium entry and protein tyrosine phosphorylation in human platelets. by Jenner (1996)
10.1182/blood.V96.10.3322.h8003322_3322_3328 / Blood. / Platelets adhere to and translocate on von Willebrand factor presented by endothelium in stimulated veins. by André (2000)

Dates

Type	When
Created	22 years, 11 months ago (Sept. 26, 2002, 7:44 p.m.)
Deposited	4 years, 2 months ago (May 28, 2021, 2:01 a.m.)
Indexed	2 days, 11 hours ago (Aug. 24, 2025, 7:01 p.m.)
Issued	22 years, 10 months ago (Oct. 15, 2002)
Published	22 years, 10 months ago (Oct. 15, 2002)
Published Print	22 years, 10 months ago (Oct. 15, 2002)

Funders 0

None

BibTeX

@article{Mazzucato_2002, title={Sequential cytoplasmic calcium signals in a 2-stage platelet activation process induced by the glycoprotein Ibα mechanoreceptor}, volume={100}, ISSN={0006-4971}, url={http://dx.doi.org/10.1182/blood-2002-02-0514}, DOI={10.1182/blood-2002-02-0514}, number={8}, journal={Blood}, publisher={American Society of Hematology}, author={Mazzucato, Mario and Pradella, Paola and Cozzi, Maria Rita and De Marco, Luigi and Ruggeri, Zaverio M.}, year={2002}, month=oct, pages={2793–2800} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        24
      ]
    ],
    "date-time": "2025-08-24T23:01:53Z",
    "timestamp": 1756076513876
  },
  "reference-count": 40,
  "publisher": "American Society of Hematology",
  "issue": "8",
  "content-domain": {
    "domain": [
      "ashpublications.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2002,
        10,
        15
      ]
    ]
  },
  "abstract": "<jats:p>We found that the interaction of platelets with immobilized von Willebrand factor (VWF) under flow induces distinct elevations of cytosolic Ca++ concentration ([Ca++]i) that are associated with sequential stages of integrin \u03b1IIb\u03b23 activation. Fluid-dynamic conditions that are compatible with the existence of tensile stress on the bonds between glycoprotein Ib\u03b1 (GPIb\u03b1) and the VWF A1 domain led to Ca++ release from intracellular stores (type \u03b1/\u03b2 peaks), which preceded stationary platelet adhesion. Raised levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate, as well as membrane-permeable calcium chelators, inhibited these [Ca++]ioscillations and prevented stable adhesion without affecting the dynamic characteristics of the typical platelet translocation on VWF mediated by GPIb\u03b1. Once adhesion was established through the integrin \u03b1IIb\u03b23, new [Ca++]i oscillations (type \u03b3) of greater amplitude and duration, and involving a transmembrane ion flux, developed in association with the recruitment of additional platelets into aggregates. Degradation of released adenosine diphosphate (ADP) to AMP or inhibition of phosphatidylinositol 3-kinase (PI3-K) prevented this response without affecting stationary adhesion and blocked aggregation. These findings indicate that an initial signal induced by stressed GPIb\u03b1-VWF bonds leads to \u03b1IIb\u03b23 activation sufficient to support localized platelet adhesion. Then, additional signals from ADP receptors and possibly ligand-occupied \u03b1IIb\u03b23, with the contribution of a pathway involving PI3-K, amplify platelet activation to the level required for aggregation. Our conclusions modify those proposed by others regarding the mechanisms that regulate signaling between GPIb\u03b1 and \u03b1IIb\u03b23 and lead to platelet adhesion and aggregation on immobilized VWF.</jats:p>",
  "DOI": "10.1182/blood-2002-02-0514",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        9,
        26
      ]
    ],
    "date-time": "2002-09-26T23:44:31Z",
    "timestamp": 1033083871000
  },
  "page": "2793-2800",
  "update-policy": "http://dx.doi.org/10.1182/blood.2019cm0000",
  "source": "Crossref",
  "is-referenced-by-count": 147,
  "title": "Sequential cytoplasmic calcium signals in a 2-stage platelet activation process induced by the glycoprotein Ib\u03b1 mechanoreceptor",
  "prefix": "10.1182",
  "volume": "100",
  "author": [
    {
      "given": "Mario",
      "family": "Mazzucato",
      "sequence": "first",
      "affiliation": [
        {
          "name": "From the Servizio Immunotrasfusionale e Analisi Cliniche, Centro di Riferimento Oncologico, Aviano, Italy; and the Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Departments of Molecular and Experimental Medicine and of Vascular Biology, Scripps Research Institute, La Jolla, CA."
        }
      ]
    },
    {
      "given": "Paola",
      "family": "Pradella",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From the Servizio Immunotrasfusionale e Analisi Cliniche, Centro di Riferimento Oncologico, Aviano, Italy; and the Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Departments of Molecular and Experimental Medicine and of Vascular Biology, Scripps Research Institute, La Jolla, CA."
        }
      ]
    },
    {
      "given": "Maria Rita",
      "family": "Cozzi",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From the Servizio Immunotrasfusionale e Analisi Cliniche, Centro di Riferimento Oncologico, Aviano, Italy; and the Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Departments of Molecular and Experimental Medicine and of Vascular Biology, Scripps Research Institute, La Jolla, CA."
        }
      ]
    },
    {
      "given": "Luigi",
      "family": "De Marco",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From the Servizio Immunotrasfusionale e Analisi Cliniche, Centro di Riferimento Oncologico, Aviano, Italy; and the Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Departments of Molecular and Experimental Medicine and of Vascular Biology, Scripps Research Institute, La Jolla, CA."
        }
      ]
    },
    {
      "given": "Zaverio M.",
      "family": "Ruggeri",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From the Servizio Immunotrasfusionale e Analisi Cliniche, Centro di Riferimento Oncologico, Aviano, Italy; and the Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Departments of Molecular and Experimental Medicine and of Vascular Biology, Scripps Research Institute, La Jolla, CA."
        }
      ]
    }
  ],
  "member": "234",
  "reference": [
    {
      "key": "2019111821325920300_B1",
      "first-page": "1",
      "article-title": "Platelets, hemostasis and thrombosis.",
      "volume-title": "Von Willebrand Factor and the Mechanisms of Platelet Function.",
      "author": "Ruggeri",
      "year": "1998"
    },
    {
      "key": "2019111821325920300_B2",
      "doi-asserted-by": "crossref",
      "first-page": "242",
      "DOI": "10.1056/NEJM199201233260406",
      "article-title": "The pathogenesis of coronary artery disease and the acute coronary syndromes (1).",
      "volume": "326",
      "author": "Fuster",
      "year": "1992",
      "journal-title": "N Engl J Med."
    },
    {
      "key": "2019111821325920300_B3",
      "doi-asserted-by": "crossref",
      "first-page": "310",
      "DOI": "10.1056/NEJM199201303260506",
      "article-title": "The pathogenesis of coronary artery disease and the acute coronary syndromes (2).",
      "volume": "326",
      "author": "Fuster",
      "year": "1992",
      "journal-title": "N Engl J Med."
    },
    {
      "key": "2019111821325920300_B4",
      "doi-asserted-by": "crossref",
      "first-page": "657",
      "DOI": "10.1016/S0092-8674(00)81607-4",
      "article-title": "Specific synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow.",
      "volume": "94",
      "author": "Savage",
      "year": "1998",
      "journal-title": "Cell."
    },
    {
      "key": "2019111821325920300_B5",
      "doi-asserted-by": "crossref",
      "first-page": "289",
      "DOI": "10.1016/S0092-8674(00)80983-6",
      "article-title": "Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor.",
      "volume": "84",
      "author": "Savage",
      "year": "1996",
      "journal-title": "Cell."
    },
    {
      "key": "2019111821325920300_B6",
      "doi-asserted-by": "crossref",
      "first-page": "172",
      "DOI": "10.1182/blood.V94.1.172.413k17_172_178",
      "article-title": "Contribution of distinct adhesive interactions to platelet aggregation in flowing blood.",
      "volume": "94",
      "author": "Ruggeri",
      "year": "1999",
      "journal-title": "Blood."
    },
    {
      "key": "2019111821325920300_B7",
      "doi-asserted-by": "crossref",
      "first-page": "7424",
      "DOI": "10.1073/pnas.82.21.7424",
      "article-title": "Interaction of purified IIB von Willebrand factor with the platelet membrane glycoprotein Ib induces fibrinogen binding to the glycoprotein IIb/IIIa complex and initiates aggregation.",
      "volume": "82",
      "author": "De Marco",
      "year": "1985",
      "journal-title": "Proc Natl Acad Sci U S A."
    },
    {
      "key": "2019111821325920300_B8",
      "doi-asserted-by": "crossref",
      "first-page": "475",
      "DOI": "10.1172/JCI113095",
      "article-title": "Type IIB von Willebrand factor with normal sialic acid content induces platelet aggregation in the absence of ristocetin: role of platelet activation, fibrinogen, and two distinct membrane receptors.",
      "volume": "80",
      "author": "De Marco",
      "year": "1987",
      "journal-title": "J Clin Invest."
    },
    {
      "key": "2019111821325920300_B9",
      "doi-asserted-by": "crossref",
      "first-page": "113",
      "DOI": "10.1182/blood.V80.1.113.113",
      "article-title": "Shear stress-induced von Willebrand factor binding to platelet glycoprotein Ib initiates calcium influx associated with aggregation.",
      "volume": "80",
      "author": "Chow",
      "year": "1992",
      "journal-title": "Blood."
    },
    {
      "key": "2019111821325920300_B10",
      "doi-asserted-by": "crossref",
      "first-page": "496",
      "DOI": "10.1055/s-0038-1651640",
      "article-title": "Transmembrane calcium influx associated with von Willebrand factor binding to GP Ib in the initiation of shear-induced platelet aggregation.",
      "volume": "69",
      "author": "Ikeda",
      "year": "1993",
      "journal-title": "Thromb Haemost."
    },
    {
      "key": "2019111821325920300_B11",
      "doi-asserted-by": "crossref",
      "first-page": "1149",
      "DOI": "10.1182/blood.V94.4.1149",
      "article-title": "Cytosolic calcium changes in a process of platelet adhesion and cohesion on a von Willebrand factor-coated surface under flow conditions.",
      "volume": "94",
      "author": "Kuwahara",
      "year": "1999",
      "journal-title": "Blood."
    },
    {
      "key": "2019111821325920300_B12",
      "doi-asserted-by": "crossref",
      "first-page": "41377",
      "DOI": "10.1074/jbc.M005590200",
      "article-title": "Synergistic adhesive interactions and signaling mechanisms operating between platelet glycoprotein Ib/IX and integrin \u03b1IIb\u03b23: studies in human platelets and transfected Chinese hamster ovary cells.",
      "volume": "275",
      "author": "Yap",
      "year": "2000",
      "journal-title": "J Biol Chem."
    },
    {
      "key": "2019111821325920300_B13",
      "doi-asserted-by": "crossref",
      "first-page": "2965",
      "DOI": "10.1074/jbc.M110070200",
      "article-title": "Distinct glycoprotein Ib/V/IX and integrin \u03b1IIb\u03b23-dependent calcium signals cooperatively regulate platelet adhesion under flow.",
      "volume": "277",
      "author": "Nesbitt",
      "year": "2002",
      "journal-title": "J Biol Chem."
    },
    {
      "key": "2019111821325920300_B14",
      "doi-asserted-by": "crossref",
      "first-page": "859",
      "DOI": "10.1016/0092-8674(91)90393-D",
      "article-title": "Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins.",
      "volume": "65",
      "author": "Lawrence",
      "year": "1991",
      "journal-title": "Cell."
    },
    {
      "key": "2019111821325920300_B15",
      "doi-asserted-by": "crossref",
      "first-page": "151",
      "DOI": "10.1182/blood.V99.1.151",
      "article-title": "Essential role for phosphoinositide 3-kinase in shear-dependent signaling between platelet glycoprotein Ib/V/IX and integrin \u03b1IIb\u03b23.",
      "volume": "99",
      "author": "Yap",
      "year": "2002",
      "journal-title": "Blood."
    },
    {
      "key": "2019111821325920300_B16",
      "doi-asserted-by": "crossref",
      "first-page": "513",
      "DOI": "10.1042/bj2690513",
      "article-title": "Use of fluo-3 to measure cytosolic Ca2+ in platelets and neutrophils: loading cells with the dye, calibration of traces, measurements in the presence of plasma, and buffering of cytosolic Ca2+.",
      "volume": "269",
      "author": "Merritt",
      "year": "1990",
      "journal-title": "Biochem J."
    },
    {
      "key": "2019111821325920300_B17",
      "doi-asserted-by": "crossref",
      "first-page": "6586",
      "DOI": "10.1074/jbc.274.10.6586",
      "article-title": "Distinct structural attributes regulating von Willebrand factor A1 domain interaction with platelet glycoprotein Ib\u03b1 under flow.",
      "volume": "274",
      "author": "Miyata",
      "year": "1999",
      "journal-title": "J Biol Chem."
    },
    {
      "key": "2019111821325920300_B18",
      "doi-asserted-by": "crossref",
      "first-page": "12579",
      "DOI": "10.1016/S0021-9258(18)67128-5",
      "article-title": "The von Willebrand factor-binding domain of platelet membrane glycoprotein Ib: characterization by monoclonal antibodies and partial amino acid sequence analysis of proteolytic fragments.",
      "volume": "261",
      "author": "Handa",
      "year": "1986",
      "journal-title": "J Biol Chem."
    },
    {
      "key": "2019111821325920300_B19",
      "doi-asserted-by": "crossref",
      "first-page": "475",
      "DOI": "10.1182/blood.V70.2.475.475",
      "article-title": "Increased surface expression of the membrane glycoprotein IIb/IIIa complex induced by platelet activation: relationship to the binding of fibrinogen and platelet aggregation.",
      "volume": "70",
      "author": "Niiya",
      "year": "1987",
      "journal-title": "Blood."
    },
    {
      "key": "2019111821325920300_B20",
      "doi-asserted-by": "crossref",
      "first-page": "412",
      "DOI": "10.1055/s-0037-1615861",
      "article-title": "Cyclic nucleotides and phosphodiesterases in platelets.",
      "volume": "82",
      "author": "Haslam",
      "year": "1999",
      "journal-title": "Thromb Haemost."
    },
    {
      "key": "2019111821325920300_B21",
      "doi-asserted-by": "crossref",
      "first-page": "472",
      "DOI": "10.1016/S1367-5931(98)80123-3",
      "article-title": "Chemotherapeutic potential of phosphodiesterase inhibitors.",
      "volume": "2",
      "author": "Perry",
      "year": "1998",
      "journal-title": "Curr Opin Chem Biol."
    },
    {
      "key": "2019111821325920300_B22",
      "doi-asserted-by": "crossref",
      "first-page": "563",
      "DOI": "10.1007/BF02285104",
      "article-title": "Correlation between theophylline concentration in plasma, erythrocytes and cantharides induces blister fluid and peak expiratory flow in asthma patients.",
      "volume": "43",
      "author": "Philip-Joet",
      "year": "1992",
      "journal-title": "Eur J Clin Pharmacol."
    },
    {
      "key": "2019111821325920300_B23",
      "doi-asserted-by": "crossref",
      "first-page": "3033",
      "DOI": "10.1074/jbc.274.5.3033",
      "article-title": "Identification of domains responsible for von Willebrand factor type VI collagen interaction mediating platelet adhesion under high flow.",
      "volume": "274",
      "author": "Mazzucato",
      "year": "1999",
      "journal-title": "J Biol Chem."
    },
    {
      "key": "2019111821325920300_B24",
      "doi-asserted-by": "crossref",
      "first-page": "18605",
      "DOI": "10.1016/S0021-9258(19)37004-8",
      "article-title": "Identification of a region in the cytoplasmic domain of the platelet membrane glycoprotein Ib-IX complex that binds to purified actin-binding protein.",
      "volume": "267",
      "author": "Andrews",
      "year": "1992",
      "journal-title": "J Biol Chem."
    },
    {
      "key": "2019111821325920300_B25",
      "doi-asserted-by": "crossref",
      "first-page": "11581",
      "DOI": "10.1074/jbc.271.19.11581",
      "article-title": "The cytoplasmic domain of the \u03b1-subunit of glycoprotein (GP) Ib mediates attachment of the entire GP Ib-IX complex to the cytoskeleton and regulates von Willebrand factor-induced changes in cell morphology.",
      "volume": "271",
      "author": "Cunningham",
      "year": "1996",
      "journal-title": "J Biol Chem."
    },
    {
      "key": "2019111821325920300_B26",
      "doi-asserted-by": "crossref",
      "first-page": "7362",
      "DOI": "10.1074/jbc.271.13.7362",
      "article-title": "Identification of a binding sequence for the 14-3-3 protein within the cytoplasmic domain of the adhesion receptor, platelet glycoprotein Ib\u03b1.",
      "volume": "271",
      "author": "Du",
      "year": "1996",
      "journal-title": "J Biol Chem."
    },
    {
      "key": "2019111821325920300_B27",
      "doi-asserted-by": "crossref",
      "first-page": "617",
      "DOI": "10.1146/annurev.pharmtox.40.1.617",
      "article-title": "14-3-3 proteins: structure, function, and regulation.",
      "volume": "40",
      "author": "Fu",
      "year": "2000",
      "journal-title": "Annu Rev Pharmacol Toxicol."
    },
    {
      "key": "2019111821325920300_B28",
      "doi-asserted-by": "crossref",
      "first-page": "16779",
      "DOI": "10.1074/jbc.275.22.16779",
      "article-title": "Signaling across the platelet adhesion receptor glycoprotein Ib-IX induces \u03b1IIb\u03b23 activation both in platelets and a transfected Chinese hamster ovary cell system.",
      "volume": "275",
      "author": "Zaffran",
      "year": "2000",
      "journal-title": "J Biol Chem."
    },
    {
      "key": "2019111821325920300_B29",
      "doi-asserted-by": "crossref",
      "first-page": "315",
      "DOI": "10.1038/361315a0",
      "article-title": "Inositol triphosphate and calcium signalling.",
      "volume": "361",
      "author": "Berridge",
      "year": "1993",
      "journal-title": "Nature."
    },
    {
      "key": "2019111821325920300_B30",
      "doi-asserted-by": "crossref",
      "first-page": "281",
      "DOI": "10.1016/0006-291X(90)91271-S",
      "article-title": "Shear stress increases inositol trisphosphate levels in human endothelial cells.",
      "volume": "170",
      "author": "Nollert",
      "year": "1990",
      "journal-title": "Biochem Biophys Res Commun."
    },
    {
      "key": "2019111821325920300_B31",
      "doi-asserted-by": "crossref",
      "first-page": "443",
      "DOI": "10.1159/000158963",
      "article-title": "Fluid shear stress stimulates membrane phospholipid metabolism in cultured human endothelial cells.",
      "volume": "29",
      "author": "Bhagyalakshmi",
      "year": "1992",
      "journal-title": "J Vasc Res."
    },
    {
      "key": "2019111821325920300_B32",
      "doi-asserted-by": "crossref",
      "first-page": "C989",
      "DOI": "10.1152/ajpcell.2000.278.5.C989",
      "article-title": "Ca2+ regulates fluid shear-induced cytoskeletal reorganization and gene expression in osteoblasts.",
      "volume": "278",
      "author": "Chen",
      "year": "2000",
      "journal-title": "Am J Physiol Cell Physiol."
    },
    {
      "key": "2019111821325920300_B33",
      "doi-asserted-by": "crossref",
      "first-page": "1366",
      "DOI": "10.1182/blood.V71.5.1366.bloodjournal7151366",
      "article-title": "Shear-induced platelet aggregation can be mediated by vWF released from platelets, as well as by exogenous large or unusually large vWF multimers, requires adenosine diphosphate, and is resistant to aspirin.",
      "volume": "71",
      "author": "Moake",
      "year": "1988",
      "journal-title": "Blood."
    },
    {
      "key": "2019111821325920300_B34",
      "doi-asserted-by": "crossref",
      "first-page": "3340",
      "DOI": "10.1182/blood.V98.12.3340",
      "article-title": "Blockade of adenosine diphosphate receptors P2Y12 and P2Y1 is required to inhibit platelet aggregation in whole blood under flow.",
      "volume": "98",
      "author": "Turner",
      "year": "2001",
      "journal-title": "Blood."
    },
    {
      "key": "2019111821325920300_B35",
      "doi-asserted-by": "crossref",
      "first-page": "27093",
      "DOI": "10.1016/S0021-9258(18)47130-X",
      "article-title": "Adhesion receptor activation of phosphatidylinositol 3-kinase: von Willebrand factor stimulates the cytoskeletal association and activation of phosphatidylinositol 3-kinase and pp60c-src in human platelets.",
      "volume": "268",
      "author": "Jackson",
      "year": "1994",
      "journal-title": "J Biol Chem."
    },
    {
      "key": "2019111821325920300_B36",
      "first-page": "15",
      "article-title": "Platelet activation by ADP: the role of ADP antagonists.",
      "volume": "32(suppl 1)",
      "author": "Gachet",
      "year": "2000",
      "journal-title": "Ann Med."
    },
    {
      "key": "2019111821325920300_B37",
      "doi-asserted-by": "crossref",
      "first-page": "2231",
      "DOI": "10.1016/S0021-9258(18)89543-6",
      "article-title": "Ca2+ transport across the platelet plasma membrane: a role for membrane glycoproteins IIb and IIIa.",
      "volume": "260",
      "author": "Brass",
      "year": "1985",
      "journal-title": "J Biol Chem."
    },
    {
      "key": "2019111821325920300_B38",
      "doi-asserted-by": "crossref",
      "first-page": "9110",
      "DOI": "10.1074/jbc.275.13.9110",
      "article-title": "Phosphoinositides are required for store-mediated calcium entry in human platelets.",
      "volume": "275",
      "author": "Rosado",
      "year": "2000",
      "journal-title": "J Biol Chem."
    },
    {
      "key": "2019111821325920300_B39",
      "doi-asserted-by": "crossref",
      "first-page": "249",
      "DOI": "10.1016/0014-5793(96)00130-5",
      "article-title": "Wortmannin inhibits store-mediated calcium entry and protein tyrosine phosphorylation in human platelets.",
      "volume": "381",
      "author": "Jenner",
      "year": "1996",
      "journal-title": "FEBS Lett."
    },
    {
      "key": "2019111821325920300_B40",
      "doi-asserted-by": "crossref",
      "first-page": "3322",
      "DOI": "10.1182/blood.V96.10.3322.h8003322_3322_3328",
      "article-title": "Platelets adhere to and translocate on von Willebrand factor presented by endothelium in stimulated veins.",
      "volume": "96",
      "author": "Andre\u0301",
      "year": "2000",
      "journal-title": "Blood."
    }
  ],
  "container-title": "Blood",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "http://ashpublications.org/blood/article-pdf/100/8/2793/1257344/h82002002793.pdf",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "syndication"
    },
    {
      "URL": "http://ashpublications.org/blood/article-pdf/100/8/2793/1257344/h82002002793.pdf",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2021,
        5,
        28
      ]
    ],
    "date-time": "2021-05-28T06:01:31Z",
    "timestamp": 1622181691000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://ashpublications.org/blood/article/100/8/2793/106401/Sequential-cytoplasmic-calcium-signals-in-a-2stage"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2002,
        10,
        15
      ]
    ]
  },
  "references-count": 40,
  "journal-issue": {
    "issue": "8",
    "published-print": {
      "date-parts": [
        [
          2002,
          10,
          15
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.1182/blood-2002-02-0514",
  "relation": {},
  "ISSN": [
    "1528-0020",
    "0006-4971"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        2002,
        10,
        15
      ]
    ]
  }
}