Gp1ba

Summary

Gene Symbol: Gp1ba
Description: glycoprotein 1b, alpha polypeptide
Alias: GP-Ib alpha, GPIba, GPIbalpha, platelet glycoprotein Ib alpha chain, glycoprotein Ibalpha
Species: mouse
Products:     Gp1ba

Top Publications

  1. Bergmeier W, Piffath C, Goerge T, Cifuni S, Ruggeri Z, Ware J, et al. The role of platelet adhesion receptor GPIbalpha far exceeds that of its main ligand, von Willebrand factor, in arterial thrombosis. Proc Natl Acad Sci U S A. 2006;103:16900-5 pubmed
    b>GPIbalpha binding to von Willebrand factor (VWF) exposed at a site of vascular injury is thought to be the first step in the formation of a hemostatic plug...
  2. Ware J, Russell S, Ruggeri Z. Cloning of the murine platelet glycoprotein Ibalpha gene highlighting species-specific platelet adhesion. Blood Cells Mol Dis. 1997;23:292-301 pubmed
    ..The results further define the structural elements necessary for the interaction of human vWF and platelets. ..
  3. Whisstock J, Shen Y, Lopez J, Andrews R, Berndt M. Molecular modeling of the seven tandem leucine-rich repeats within the ligand-binding region of platelet glycoprotein Ib alpha. Thromb Haemost. 2002;87:329-33 pubmed
    ..This provides the basis for relating these genetic lesions to abnormal function of the receptor. ..
  4. Kanaji T, Russell S, Ware J. Amelioration of the macrothrombocytopenia associated with the murine Bernard-Soulier syndrome. Blood. 2002;100:2102-7 pubmed
    ..These results provide in vivo insights into the structural elements of the GP Ibalpha subunit that contribute to normal megakaryocyte maturation and thrombopoiesis. ..
  5. Konstantinides S, Ware J, Marchese P, Almus Jacobs F, Loskutoff D, Ruggeri Z. Distinct antithrombotic consequences of platelet glycoprotein Ibalpha and VI deficiency in a mouse model of arterial thrombosis. J Thromb Haemost. 2006;4:2014-21 pubmed
    ..Components of the extracellular matrix may elicit a thrombogenic response in the absence of GP VI but not GP Ibalpha. ..
  6. Fujita H, Hashimoto Y, Russell S, Zieger B, Ware J. In vivo expression of murine platelet glycoprotein Ibalpha. Blood. 1998;92:488-95 pubmed
  7. Yougbaré I, Lang S, Yang H, Chen P, Zhao X, Tai W, et al. Maternal anti-platelet β3 integrins impair angiogenesis and cause intracranial hemorrhage. J Clin Invest. 2015;125:1545-56 pubmed publisher
    ..Additionally, our results indicate that maternal IVIG therapy can effectively prevent this devastating disorder. ..
  8. Hillgruber C, Steingräber A, Poppelmann B, Denis C, Ware J, Vestweber D, et al. Blocking von Willebrand factor for treatment of cutaneous inflammation. J Invest Dermatol. 2014;134:77-86 pubmed publisher
    ..Of particular importance, anti-VWF treatment was effective both in prophylactic and therapeutic administration. Thus, VWF represents a promising target for the treatment of cutaneous inflammation, e.g., leukocytoclastic vasculitis. ..
  9. Yang W, Gutierrez N, Wang L, Ellsworth B, Wang C. Synergistic activation of the Mc2r promoter by FOXL2 and NR5A1 in mice. Biol Reprod. 2010;83:842-51 pubmed publisher
    ..These results suggest that the interplay between FOXL2 and NR5A1 on the Mc2r promoter functions as a novel mechanism for regulating MC2R-mediated cell signaling as well as steroidogenesis in adrenal glands. ..

Scientific Experts

More Information

Publications53

  1. Guerrero J, Kyei M, Russell S, Liu J, Gartner T, Storrie B, et al. Visualizing the von Willebrand factor/glycoprotein Ib-IX axis with a platelet-type von Willebrand disease mutation. Blood. 2009;114:5541-6 pubmed publisher
    ..Visualization of the receptor/ligand interaction and characterization of a severe antithrombotic phenotype provide a new understanding on the molecular basis of bleeding associated with the PT-VWD phenotype. ..
  2. Iannacone M, Sitia G, Isogawa M, Whitmire J, Marchese P, Chisari F, et al. Platelets prevent IFN-alpha/beta-induced lethal hemorrhage promoting CTL-dependent clearance of lymphocytic choriomeningitis virus. Proc Natl Acad Sci U S A. 2008;105:629-34 pubmed publisher
  3. Aktas B, Pozgajova M, Bergmeier W, Sunnarborg S, Offermanns S, Lee D, et al. Aspirin induces platelet receptor shedding via ADAM17 (TACE). J Biol Chem. 2005;280:39716-22 pubmed
    ..whole blood, aspirin, but not its metabolite salicylic acid, induced dose-dependent shedding of human and murine GPIbalpha and GPV from the platelet surface, whereas other glycoproteins remained unaffected by this treatment...
  4. Ware J, Russell S, Ruggeri Z. Generation and rescue of a murine model of platelet dysfunction: the Bernard-Soulier syndrome. Proc Natl Acad Sci U S A. 2000;97:2803-8 pubmed
    ..Thus, an in vivo model is defined for analysis of the human GP Ib-IX-V receptor and its role in the processes performed exclusively by megakaryocytes and platelets. ..
  5. Watters J, Dietrich W. Genetic, physical, and transcript map of the Ltxs1 region of mouse chromosome 11. Genomics. 2001;73:223-31 pubmed
    ..Additionally, a region of 100 kb or more is deleted in the Ltxs1 interval of some strains. Our genetic, physical, and transcript map provides an important resource for the molecular cloning of Ltxs1. ..
  6. Nishimoto T, Satoh T, Simpson E, Ni H, Kuwana M. Predominant autoantibody response to GPIb/IX in a regulatory T-cell-deficient mouse model for immune thrombocytopenia. J Thromb Haemost. 2013;11:369-72 pubmed publisher
  7. Cunin P, Penke L, Thon J, Monach P, Jones T, Chang M, et al. Megakaryocytes compensate for Kit insufficiency in murine arthritis. J Clin Invest. 2017;127:1714-1724 pubmed publisher
    ..These findings identify functional redundancy among Kit-dependent hematopoietic lineages and establish an unanticipated capacity of megakaryocytes to mediate IL-1-driven systemic inflammatory disease. ..
  8. Barr J, Chauhan A, Schaeffer G, Hansen J, Motto D. Red blood cells mediate the onset of thrombosis in the ferric chloride murine model. Blood. 2013;121:3733-41 pubmed publisher
    ..These findings illuminate the mechanisms of FeCl(3)-mediated thrombosis and reveal a previously unrecognized ability of RBCs to participate in thrombosis by mediating platelet adhesion to the intact endothelial surface. ..
  9. Pang L, Xue H, Szalai G, Wang X, Wang Y, Watson D, et al. Maturation stage-specific regulation of megakaryopoiesis by pointed-domain Ets proteins. Blood. 2006;108:2198-206 pubmed
    ..In concert, these data reveal disparate, but overlapping, functions of Ets transcription factors at distinct stages of megakaryocyte maturation. ..
  10. Yin H, Stojanovic Terpo A, Xu W, Corken A, Zakharov A, Qian F, et al. Role for platelet glycoprotein Ib-IX and effects of its inhibition in endotoxemia-induced thrombosis, thrombocytopenia, and mortality. Arterioscler Thromb Vasc Biol. 2013;33:2529-37 pubmed publisher
    ..These data indicate an important role for the platelet adhesion receptor GPIb-IX in LPS-induced thrombosis and thrombocytopenia, and suggest the potential of targeting GPIb as an antiplatelet strategy in managing endotoxemia. ..
  11. Andre P, Denis C, Ware J, Saffaripour S, Hynes R, Ruggeri Z, et al. Platelets adhere to and translocate on von Willebrand factor presented by endothelium in stimulated veins. Blood. 2000;96:3322-8 pubmed
    ..The adhesion was mediated by platelet glycoprotein Ibalpha (GPIbalpha) because the adhesion of murine platelets expressing exclusively the human GPIbalpha could be ..
  12. Mason K, Carpinelli M, Fletcher J, Collinge J, Hilton A, Ellis S, et al. Programmed anuclear cell death delimits platelet life span. Cell. 2007;128:1173-86 pubmed
  13. Chen J, Zhou H, Diacovo A, Zheng X, Emsley J, Diacovo T. Exploiting the kinetic interplay between GPIbα-VWF binding interfaces to regulate hemostasis and thrombosis. Blood. 2014;124:3799-807 pubmed publisher
  14. Guidotti L, Inverso D, Sironi L, Di Lucia P, Fioravanti J, Ganzer L, et al. Immunosurveillance of the liver by intravascular effector CD8(+) T cells. Cell. 2015;161:486-500 pubmed publisher
    ..These findings reveal the dynamic behavior whereby CD8 TE control hepatotropic pathogens and suggest how liver fibrosis might reduce CD8 TE immune surveillance toward infected or transformed hepatocytes. ..
  15. Marx I, Christophe O, Lenting P, Rupin A, Vallez M, Verbeuren T, et al. Altered thrombus formation in von Willebrand factor-deficient mice expressing von Willebrand factor variants with defective binding to collagen or GPIIbIIIa. Blood. 2008;112:603-9 pubmed publisher
    ..Our observations suggest that targeting the VWF-collagen or VWF-GPIIbIIIa interactions could be an interesting alternative for new antithrombotic strategies. ..
  16. Li C, Piran S, Chen P, Lang S, Zarpellon A, Jin J, et al. The maternal immune response to fetal platelet GPIb? causes frequent miscarriage in mice that can be prevented by intravenous IgG and anti-FcRn therapies. J Clin Invest. 2011;121:4537-47 pubmed publisher
    ..These results suggest that a similar pathology may have masked the severity and frequency of human anti-GPIb?-mediated FNIT, but also point to possible therapeutic interventions. ..
  17. Li J, Kim K, Hahm E, Molokie R, Hay N, Gordeuk V, et al. Neutrophil AKT2 regulates heterotypic cell-cell interactions during vascular inflammation. J Clin Invest. 2014;124:1483-96 pubmed publisher
    ..Our results provide evidence that neutrophil AKT2 regulates ?M?2 integrin function and suggest that AKT2 is important for neutrophil recruitment and neutrophil-platelet interactions under thromboinflammatory conditions such as SCD. ..
  18. Chandraratne S, von Bruehl M, Pagel J, Stark K, Kleinert E, Konrad I, et al. Critical role of platelet glycoprotein ibα in arterial remodeling. Arterioscler Thromb Vasc Biol. 2015;35:589-97 pubmed publisher
    ..Thus, GPIbα-mediated interactions between platelets and endothelial cells, as well as leukocytes, support innate immune cell recruitment and promote arteriogenesis-establishing platelets as critical players in this process. ..
  19. Suva L, Hartman E, Dilley J, Russell S, Akel N, Skinner R, et al. Platelet dysfunction and a high bone mass phenotype in a murine model of platelet-type von Willebrand disease. Am J Pathol. 2008;172:430-9 pubmed publisher
    ..These studies provide new insights into the relationship between the regulation of megakaryocytopoiesis and bone mass. ..
  20. Li J, van der Wal D, Zhu G, Xu M, Yougbare I, Ma L, et al. Desialylation is a mechanism of Fc-independent platelet clearance and a therapeutic target in immune thrombocytopenia. Nat Commun. 2015;6:7737 pubmed publisher
    ..These findings shed light on Fc-independent cytopenias, designating desialylation as a potential diagnostic biomarker and therapeutic target in the treatment of refractory ITP. ..
  21. Strassel C, Nonne C, Eckly A, David T, Leon C, Freund M, et al. Decreased thrombotic tendency in mouse models of the Bernard-Soulier syndrome. Arterioscler Thromb Vasc Biol. 2007;27:241-7 pubmed
    ..This study provides in vivo evidence of a decreased thrombotic tendency linked to defective platelet GPIb-V-IX in mouse models of Bernard-Soulier syndrome. ..
  22. Mehta A, Mohammed B, Martin E, Brophy D, Gailani D, Desai U. Allosterism-based simultaneous, dual anticoagulant and antiplatelet action: allosteric inhibitor targeting the glycoprotein Ibα-binding and heparin-binding site of thrombin. J Thromb Haemost. 2016;14:828-38 pubmed publisher
    ..Overall, this study highlights the promise of the allosteric inhibition approach, and presents SbO4L as a novel anticoagulant with potentially reduced bleeding side effects. ..
  23. Poujol C, Ware J, Nieswandt B, Nurden A, Nurden P. Absence of GPIbalpha is responsible for aberrant membrane development during megakaryocyte maturation: ultrastructural study using a transgenic model. Exp Hematol. 2002;30:352-60 pubmed
    ..Molecular defects in the genes for GPIbalpha, GPIbbeta, and GPIX give rise to the Bernard-Soulier syndrome, in which thrombocytopenia and giant platelets ..
  24. Uff S, Clemetson J, Harrison T, Clemetson K, Emsley J. Crystal structure of the platelet glycoprotein Ib(alpha) N-terminal domain reveals an unmasking mechanism for receptor activation. J Biol Chem. 2002;277:35657-63 pubmed
    ..Using molecular docking of the GPIb and vWF-A1 crystal structures, we were also able to model the GPIb.vWF-A1 complex. ..
  25. Kaplan Z, Zarpellon A, Alwis I, Yuan Y, McFadyen J, Ghasemzadeh M, et al. Thrombin-dependent intravascular leukocyte trafficking regulated by fibrin and the platelet receptors GPIb and PAR4. Nat Commun. 2015;6:7835 pubmed publisher
    ..Dysregulation of this checkpoint mechanism is likely to contribute to the development of thromboinflammatory disorders. ..
  26. Strassel C, Bull A, Moog S, Receveur N, Mallo L, Mangin P, et al. Lentiviral gene rescue of a Bernard-Soulier mouse model to study platelet glycoprotein Ibβ function. J Thromb Haemost. 2016;14:1470-9 pubmed publisher
    ..These results highlight the utility of this lentiviral strategy for the structure-function evaluation of GPIb-IX in platelets. ..
  27. Zhou H, Ran Y, Da Q, Shaw T, Shang D, Reddy A, et al. Defective Association of the Platelet Glycoprotein Ib-IX Complex with the Glycosphingolipid-Enriched Membrane Domain Inhibits Murine Thrombus and Atheroma Formation. J Immunol. 2016;197:288-95 pubmed publisher
    ..To our knowledge, these observations provide the first in vivo evidence showing that the membrane GEM is physiologically and pathophysiologically critical in the function of the glycoprotein Ib-IX complex. ..
  28. Wei S, Wang H, Zhang G, Lu Y, An X, Ren S, et al. Platelet I?B kinase-? deficiency increases mouse arterial neointima formation via delayed glycoprotein Ib? shedding. Arterioscler Thromb Vasc Biol. 2013;33:241-8 pubmed publisher
    ..The transcription factor nuclear factor-?B is a critical molecule in platelet activation. Here, we investigated the role of the platelet nuclear factor-?B pathway in forming arterial neointima after arterial injury...
  29. Kanaji T, Russell S, Cunningham J, Izuhara K, Fox J, Ware J. Megakaryocyte proliferation and ploidy regulated by the cytoplasmic tail of glycoprotein Ibalpha. Blood. 2004;104:3161-8 pubmed
    ..Using a Gp1ba(-/-) mouse colony, we compared the rescued phenotypes produced by a wild-type human GP Ibalpha allele or a similar ..
  30. Kasirer Friede A, Moran B, Nagrampa Orje J, Swanson K, Ruggeri Z, Schraven B, et al. ADAP is required for normal alphaIIbbeta3 activation by VWF/GP Ib-IX-V and other agonists. Blood. 2007;109:1018-25 pubmed
    ..These studies establish ADAP as a component of inside-out signaling pathways that couple GP Ib-IX-V and other platelet agonist receptors to alphaIIbbeta3 activation. ..
  31. Verschoor A, Neuenhahn M, Navarini A, Graef P, Plaumann A, Seidlmeier A, et al. A platelet-mediated system for shuttling blood-borne bacteria to CD8?+ dendritic cells depends on glycoprotein GPIb and complement C3. Nat Immunol. 2011;12:1194-201 pubmed publisher
    ..Other gram-positive bacteria also were rapidly tagged by platelets, revealing a broadly active shuttling mechanism for systemic bacteria. ..
  32. Li Y, Lu J, Prochownik E. Modularity of the oncoprotein-like properties of platelet glycoprotein Ibalpha. J Biol Chem. 2009;284:1410-8 pubmed publisher
    Glycoprotein Ib alpha (GpIbalpha), a trans-membrane glycoprotein, is expressed on the surface of megakaryocytes and platelets, where, in association with glycoprotein Ib beta, glycoprotein V, and glycoprotein IX, it normally forms the ..
  33. Reheman A, Yang H, Zhu G, Jin W, He F, Spring C, et al. Plasma fibronectin depletion enhances platelet aggregation and thrombus formation in mice lacking fibrinogen and von Willebrand factor. Blood. 2009;113:1809-17 pubmed publisher
    ..inhibited by our newly developed mouse anti-mouse beta(3) integrin antibodies but was not affected by anti-mouse GPIbalpha antibodies...
  34. de la Motte C, Nigro J, Vasanji A, Rho H, Kessler S, Bandyopadhyay S, et al. Platelet-derived hyaluronidase 2 cleaves hyaluronan into fragments that trigger monocyte-mediated production of proinflammatory cytokines. Am J Pathol. 2009;174:2254-64 pubmed publisher
    ..The platelet may thus provide an interface between acute and chronic inflammation, wound healing, and their subsequent fibrotic responses. ..
  35. Cosemans J, Schols S, Stefanini L, de Witt S, Feijge M, Hamulyak K, et al. Key role of glycoprotein Ib/V/IX and von Willebrand factor in platelet activation-dependent fibrin formation at low shear flow. Blood. 2011;117:651-60 pubmed publisher
    ..This process can be relevant in hemostasis and the manifestation of von Willebrand disease. ..
  36. Boulaftali Y, Hess P, Getz T, Cholka A, Stolla M, Mackman N, et al. Platelet ITAM signaling is critical for vascular integrity in inflammation. J Clin Invest. 2013;123:908-16 pubmed publisher
  37. Jansen A, Josefsson E, Rumjantseva V, Liu Q, Falet H, Bergmeier W, et al. Desialylation accelerates platelet clearance after refrigeration and initiates GPIb? metalloproteinase-mediated cleavage in mice. Blood. 2012;119:1263-73 pubmed publisher
    ..Desialylation of platelet VWFR therefore triggers platelet clearance and primes GPIb? and GPV for MP-dependent cleavage. ..
  38. Yang H, Lang S, Zhai Z, Li L, Kahr W, Chen P, et al. Fibrinogen is required for maintenance of platelet intracellular and cell-surface P-selectin expression. Blood. 2009;114:425-36 pubmed publisher
    ..Since human fibrinogen levels vary significantly in normal and diseased populations, P-selectin as an activation marker on platelets should be used with caution. ..
  39. Le Béhot A, Gauberti M, Martinez de Lizarrondo S, Montagne A, Lemarchand E, Repesse Y, et al. GpIb?-VWF blockade restores vessel patency by dissolving platelet aggregates formed under very high shear rate in mice. Blood. 2014;123:3354-63 pubmed publisher
  40. Jain S, Zuka M, Liu J, Russell S, Dent J, Guerrero J, et al. Platelet glycoprotein Ib alpha supports experimental lung metastasis. Proc Natl Acad Sci U S A. 2007;104:9024-8 pubmed
    ..Our results support the hypothesis that platelet GP Ib-IX functions that support normal hemostasis or pathologic thrombosis also contribute to tumor malignancy. ..
  41. Schleicher R, Reichenbach F, Kraft P, Kumar A, Lescan M, Todt F, et al. Platelets induce apoptosis via membrane-bound FasL. Blood. 2015;126:1483-93 pubmed publisher
    ..Because apoptosis secondary to injury prevents inflammation, our findings describe a novel mechanism on how PLTs contribute to tissue homeostasis. ..
  42. Kanaji T, Kanaji S, Montgomery R, Patel S, Newman P. Platelet hyperreactivity explains the bleeding abnormality and macrothrombocytopenia in a murine model of sitosterolemia. Blood. 2013;122:2732-42 pubmed publisher
    ..Intercalation of plant sterols into the plasma membrane therefore results in dysregulation of multiple platelet activation pathways, leading to macrothrombocytopenia and bleeding. ..
  43. Koltsova E, Sundd P, Zarpellon A, Ouyang H, Mikulski Z, Zampolli A, et al. Genetic deletion of platelet glycoprotein Ib alpha but not its extracellular domain protects from atherosclerosis. Thromb Haemost. 2014;112:1252-63 pubmed publisher
    ..Thus, atherosclerosis reduction in mice lacking GPIb? may not result from the defective GPIb?-ligand binding, but more likely is a consequence of functional defects of GPIb?-/- platelets and reduced blood platelet counts. ..
  44. Kanaji T, Ware J, Okamura T, Newman P. GPIb? regulates platelet size by controlling the subcellular localization of filamin. Blood. 2012;119:2906-13 pubmed publisher
    ..Taken together, these data demonstrate that coordinated expression of GPIb? and filamin is required for efficient trafficking of either protein to the cell surface, and for production of normal-sized platelets. ..