platelet glycoprotein gpib ix complex


Summary: Platelet membrane glycoprotein complex essential for normal platelet adhesion and clot formation at sites of vascular injury. It is composed of three polypeptides, GPIb alpha, GPIb beta, and GPIX. Glycoprotein Ib functions as a receptor for von Willebrand factor and for thrombin. Congenital deficiency of the GPIb-IX complex results in Bernard-Soulier syndrome. The platelet glycoprotein GPV associates with GPIb-IX and is also absent in Bernard-Soulier syndrome.

Top Publications

  1. Hoffmeister K, Josefsson E, Isaac N, Clausen H, Hartwig J, Stossel T. Glycosylation restores survival of chilled blood platelets. Science. 2003;301:1531-4 pubmed
    ..Platelet-associated galactosyltransferase produces efficient galactosylation when uridine diphosphate-galactose is added, affording a potentially simple method for storing platelets in the cold. ..
  2. Strassel C, David T, Eckly A, Baas M, Moog S, Ravanat C, et al. Synthesis of GPIb beta with novel transmembrane and cytoplasmic sequences in a Bernard-Soulier patient resulting in GPIb-defective signaling in CHO cells. J Thromb Haemost. 2006;4:217-28 pubmed
  3. Bergmeier W, Piffath C, Cheng G, Dole V, Zhang Y, von Andrian U, et al. Tumor necrosis factor-alpha-converting enzyme (ADAM17) mediates GPIbalpha shedding from platelets in vitro and in vivo. Circ Res. 2004;95:677-83 pubmed
    ..In conclusion, our data demonstrate that TACE is expressed in platelets and that it is the key enzyme mediating shedding of GPIbalpha. ..
  4. Gardiner E, Karunakaran D, Shen Y, Arthur J, Andrews R, Berndt M. Controlled shedding of platelet glycoprotein (GP)VI and GPIb-IX-V by ADAM family metalloproteinases. J Thromb Haemost. 2007;5:1530-7 pubmed
    ..These findings suggest surface levels of GPVI, GPIbalpha and GPV may be controlled by distinct mechanisms involving ADAM10 and/or ADAM17. ..
  5. Sachs U, Kroll H, Matzdorff A, Berghöfer H, Lopez J, Santoso S. Bernard-Soulier syndrome due to the homozygous Asn-45Ser mutation in GPIX: an unexpected, frequent finding in Germany. Br J Haematol. 2003;123:127-31 pubmed
    ..Because BSS patients are likely to be misdiagnosed with ITP, treatment-resistant ITP patients should be re-evaluated thoroughly. Asn-45Ser genotyping may be a helpful tool for differential diagnosis. ..
  6. Kunishima S, Imai T, Hamaguchi M, Saito H. Novel heterozygous missense mutation in the second leucine rich repeat of GPIbalpha affects GPIb/IX/V expression and results in macrothrombocytopenia in a patient initially misdiagnosed with idiopathic thrombocytopenic purpura. Eur J Haematol. 2006;76:348-55 pubmed
    ..These findings suggest that null expression of the mutant GPIbalpha causes decreased density of the complex and results in macrothrombocytopenia. ..
  7. Liang H, Morel Kopp M, Clemetson J, Clemetson K, Kekomaki R, Kroll H, et al. A common ancestral glycoprotein (GP) 9 1828A>G (Asn45Ser) gene mutation occurring in European families from Australia and Northern Europe with Bernard-Soulier Syndrome (BSS). Thromb Haemost. 2005;94:599-605 pubmed
    ..Additional members from these 'atypical' lineages would need to be screened to resolve this question. ..
  8. Garner C, Best S, Menzel S, Rooks H, Spector T, Thein S. Two candidate genes for low platelet count identified in an Asian Indian kindred by genome-wide linkage analysis: glycoprotein IX and thrombopoietin. Eur J Hum Genet. 2006;14:101-8 pubmed
    ..The results suggest that two QTLs on chromosome 3q influence platelet count variation in the Asian Indian kindred, with the GPIX transmembrane mutation and the 3' UTR SNP in THPO being strong candidates. ..
  9. Othman M, Notley C, Lavender F, White H, Byrne C, Lillicrap D, et al. Identification and functional characterization of a novel 27-bp deletion in the macroglycopeptide-coding region of the GPIBA gene resulting in platelet-type von Willebrand disease. Blood. 2005;105:4330-6 pubmed
    ..The mutation provides a molecular basis for the PT-VWD phenotype and supports a role for the macroglycopeptide region in receptor function. ..

More Information


  1. Watanabe R, Ishibashi T, Saitoh Y, Shichishima T, Maruyama Y, Enomoto Y, et al. Bernard-soulier syndrome with a homozygous 13 base pair deletion in the signal peptide-coding region of the platelet glycoprotein Ib(beta) gene. Blood Coagul Fibrinolysis. 2003;14:387-94 pubmed
    ..The molecular defects of this family would help understand the relevance of GPIb(beta) for complex formation of the glycoprotein Ib/IX/V receptor. ..
  2. Wang Z, Zhao X, Duan W, Fu J, Lu M, Wang G, et al. A novel mutation in the transmembrane region of glyco-protein IX associated with Bernard-Soulier syndrome. Thromb Haemost. 2004;92:606-13 pubmed
  3. Canobbio I, Balduini C, Torti M. Signalling through the platelet glycoprotein Ib-V-IX complex. Cell Signal. 2004;16:1329-44 pubmed
  4. González Manchón C, Butta N, Iruín G, Alonso S, Ayuso M, Parrilla R. Disruption of the Cys5-Cys7 disulfide bridge in the platelet glycoprotein Ibbeta prevents the normal maturation and surface exposure of GPIb-IX complexes. Thromb Haemost. 2003;90:456-64 pubmed
  5. Kasirer Friede A, Cozzi M, Mazzucato M, De Marco L, Ruggeri Z, Shattil S. Signaling through GP Ib-IX-V activates alpha IIb beta 3 independently of other receptors. Blood. 2004;103:3403-11 pubmed
    ..These data establish that GP Ib-IX-V itself can signal to activate alpha IIb beta 3, through sequential actions of Src kinases, Ca(2+) oscillations, and PI 3-kinase/PKC. ..
  6. Tang J, Stern Nezer S, Liu P, Matyakhina L, Riordan M, Luban N, et al. Mutation in the leucine-rich repeat C-flanking region of platelet glycoprotein Ib beta impairs assembly of von Willebrand factor receptor. Thromb Haemost. 2004;92:75-88 pubmed
  7. Strassel C, Alessi M, Juhan Vague I, Cazenave J, Lanza F. A 13 base pair deletion in the GPIbbeta gene in a second unrelated Bernard-Soulier family due to slipped mispairing between direct repeats. J Thromb Haemost. 2004;2:1663-5 pubmed
  8. Bergmeier W, Burger P, Piffath C, Hoffmeister K, Hartwig J, Nieswandt B, et al. Metalloproteinase inhibitors improve the recovery and hemostatic function of in vitro-aged or -injured mouse platelets. Blood. 2003;102:4229-35 pubmed
    ..Surface expression of GPIbalpha might be a powerful marker to determine the quality of platelet concentrates, because it reflects metalloproteinase activity in vitro. ..
  9. Drouin J, Carson N, Laneuville O. Compound heterozygosity for a novel nine-nucleotide deletion and the Asn45Ser missense mutation in the glycoprotein IX gene in a patient with Bernard-Soulier syndrome. Am J Hematol. 2005;78:41-8 pubmed
    ..Our findings suggest that the additive effects of both mutations in the GPIX gene are responsible for the BSS phenotype of the patient. ..
  10. Rabie T, Strehl A, Ludwig A, Nieswandt B. Evidence for a role of ADAM17 (TACE) in the regulation of platelet glycoprotein V. J Biol Chem. 2005;280:14462-8 pubmed
    ..These results demonstrate that GPV is cleaved upon agonist-induced platelet activation and show that ADAM17 is the major enzyme mediating this process. ..
  11. 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
    ..Thus, GPIbalpha contributes to arterial thrombosis by important adhesion mechanisms independent of the binding to VWF. ..
  12. Lavenu Bombled C, Izac B, Legrand F, Cambot M, Vigier A, Masse J, et al. Glycoprotein Ibalpha promoter drives megakaryocytic lineage-restricted expression after hematopoietic stem cell transduction using a self-inactivating lentiviral vector. Stem Cells. 2007;25:1571-7 pubmed
    ..Disclosure of potential conflicts of interest is found at the end of this article. ..
  13. Romo G, Dong J, Schade A, Gardiner E, Kansas G, Li C, et al. The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin. J Exp Med. 1999;190:803-14 pubmed
    ..Thus, the GP Ib-IX-V complex mediates platelet attachment to both subendothelium and activated endothelium. ..
  14. Koskela S, Partanen J, Salmi T, Kekomaki R. Molecular characterization of two mutations in platelet glycoprotein (GP) Ib alpha in two Finnish Bernard-Soulier syndrome families. Eur J Haematol. 1999;62:160-8 pubmed
    ..Interestingly, both mutations have independently been found in three other families in previous reports, suggesting their ancient age or mutational 'hot spot'. ..
  15. Hess D, Schaller J, Rickli E, Clemetson K. Identification of the disulphide bonds in human platelet glycocalicin. Eur J Biochem. 1991;199:389-93 pubmed
    ..The position and linkage of these two disulphide bonds are now determined to be 209-248 and 211-264 and the relevance of this double-loop structure for glycoprotein Ib/IX function is discussed. ..
  16. Baglia F, Badellino K, Li C, Lopez J, Walsh P. Factor XI binding to the platelet glycoprotein Ib-IX-V complex promotes factor XI activation by thrombin. J Biol Chem. 2002;277:1662-8 pubmed
    ..Thus, factor XI binds to the GP Ib-IX-V complex, promoting its activation by thrombin. ..
  17. Hillmann A, Nurden A, Nurden P, Combrie R, Claeyssens S, Moran N, et al. A novel hemizygous Bernard-Soulier Syndrome (BSS) mutation in the amino terminal domain of glycoprotein (GP)Ibbeta--platelet characterization and transfection studies. Thromb Haemost. 2002;88:1026-32 pubmed
  18. Moran N, Morateck P, Deering A, Ryan M, Montgomery R, Fitzgerald D, et al. Surface expression of glycoprotein ib alpha is dependent on glycoprotein ib beta: evidence from a novel mutation causing Bernard-Soulier syndrome. Blood. 2000;96:532-9 pubmed
    ..Thus, we found that GPIbbeta affects the surface expression of the GPIb-IX complex by failing to support the insertion of GPIb alpha and GPIX into the platelet membrane. (Blood. 2000;96:532-539) ..
  19. Rivera C, Villagra J, Riordan M, Williams S, Lindstrom K, Rick M. Identification of a new mutation in platelet glycoprotein IX (GPIX) in a patient with Bernard-Soulier syndrome. Br J Haematol. 2001;112:105-8 pubmed
  20. Kunishima S, Tomiyama Y, Honda S, Fukunishi M, Hara J, Inoue C, et al. Homozygous Pro74-->Arg mutation in the platelet glycoprotein Ibbeta gene associated with Bernard-Soulier syndrome. Thromb Haemost. 2000;84:112-7 pubmed
    ..The mutant GPIbbeta was normally transcribed. Transient transfection studies confirmed that mutant GPIbbeta impairs surface expression of GPIb/IX, showing that the mutation is responsible for a BSS phenotype observed in the patient. ..
  21. Fujita H, Hashimoto Y, Russell S, Zieger B, Ware J. In vivo expression of murine platelet glycoprotein Ibalpha. Blood. 1998;92:488-95 pubmed
  22. Emsley J, Cruz M, Handin R, Liddington R. Crystal structure of the von Willebrand Factor A1 domain and implications for the binding of platelet glycoprotein Ib. J Biol Chem. 1998;273:10396-401 pubmed
    ..A possible pathway for propagating structural changes from the regulatory region to the ligand-binding surface is discussed. ..
  23. Kurokawa Y, Ishida F, Kamijo T, Kunishima S, Kenny D, Kitano K, et al. A missense mutation (Tyr88 to Cys) in the platelet membrane glycoprotein Ibbeta gene affects GPIb/IX complex expression--Bernard-Soulier syndrome in the homozygous form and giant platelets in the heterozygous form. Thromb Haemost. 2001;86:1249-56 pubmed
    ..Tyr88 in the GPIbbeta gene plays a significant role in the GPIb/IX expression; the defect causes BSS in a homozygous form and possibly giant platelets in a heterozygous form. ..
  24. Kunishima S, Matsushita T, Ito T, Kamiya T, Saito H. Novel nonsense mutation in the platelet glycoprotein Ibbeta gene associated with Bernard-Soulier syndrome. Am J Hematol. 2002;71:279-84 pubmed
  25. Lanza F, De La Salle C, Baas M, Schwartz A, Boval B, Cazenave J, et al. A Leu7Pro mutation in the signal peptide of platelet glycoprotein (GP)IX in a case of Bernard-Soulier syndrome abolishes surface expression of the GPIb-V-IX complex. Br J Haematol. 2002;118:260-6 pubmed
    ..This provides further evidence for a critical role of GPIX in controlling biosynthesis of the GPIb-IX complex. ..
  26. Savage B, Saldivar E, Ruggeri Z. Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor. Cell. 1996;84:289-97 pubmed
    ..This eventually allows activated alpha IIb beta 3 to arrest platelets onto vWF under conditions not permissive of direct binding to fibrinogen. The coupling of these different functions may be crucial for thrombogenesis. ..
  27. Kunishima S, Lopez J, Kobayashi S, Imai N, Kamiya T, Saito H, et al. Missense mutations of the glycoprotein (GP) Ib beta gene impairing the GPIb alpha/beta disulfide linkage in a family with giant platelet disorder. Blood. 1997;89:2404-12 pubmed
    ..Furthermore, the phenotype caused by mutations in the subunits of the GPIb/IX complex could span the spectrum from a normal phenotype, to isolated GPD, to a full-blown bleeding disorder, such as Bernard-Soulier syndrome. ..
  28. Berndt M, Shen Y, Dopheide S, Gardiner E, Andrews R. The vascular biology of the glycoprotein Ib-IX-V complex. Thromb Haemost. 2001;86:178-88 pubmed
    ..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. ..
  29. Kenny D, Morateck P, Gill J, Montgomery R. The critical interaction of glycoprotein (GP) IBbeta with GPIX-a genetic cause of Bernard-Soulier syndrome. Blood. 1999;93:2968-75 pubmed
    ..The interaction of GPIbbeta with GPIX is essential for the functional expression of GPIbalpha. ..
  30. Miyazaki R, Ogata H, Kobayashi Y. Requirement of thrombopoietin-induced activation of ERK for megakaryocyte differentiation and of p38 for erythroid differentiation. Ann Hematol. 2001;80:284-91 pubmed
    ..These results indicate that activation of extracellular-signal-regulated kinase (ERK) is required for TPO-induced megakaryocyte differentiation and that p38 is required for TPO-induced erythroid differentiation. ..
  31. Ruggeri Z, Dent J, Saldivar E. Contribution of distinct adhesive interactions to platelet aggregation in flowing blood. Blood. 1999;94:172-8 pubmed
    ..The specific function of distinct adhesion pathways in response to changing hemodynamic conditions helps to explain hemostatic and thrombotic processes. ..
  32. Savoia A, Balduini C, Savino M, Noris P, del Vecchio M, Perrotta S, et al. Autosomal dominant macrothrombocytopenia in Italy is most frequently a type of heterozygous Bernard-Soulier syndrome. Blood. 2001;97:1330-5 pubmed
    ..Thus, the diagnosis of heterozygous BSS must always be suspected in patients with inherited thrombocytopenia and platelet macrocytosis. ..
  33. Canfield V, Ozols J, Nugent D, Roth G. Isolation and characterization of the alpha and beta chains of human platelet glycoprotein Ib. Biochem Biophys Res Commun. 1987;147:526-34 pubmed
    ..These studies outline a useful approach to isolate and characterize the individual chains of GPIb. ..
  34. Huizinga E, Tsuji S, Romijn R, Schiphorst M, de Groot P, Sixma J, et al. Structures of glycoprotein Ibalpha and its complex with von Willebrand factor A1 domain. Science. 2002;297:1176-9 pubmed
    ..These detailed insights into the initial interactions in platelet adhesion are relevant to the development of antithrombotic drugs. ..
  35. Yagi M, Edelhoff S, Disteche C, Roth G. Human platelet glycoproteins V and IX: mapping of two leucine-rich glycoprotein genes to chromosome 3 and analysis of structures. Biochemistry. 1995;34:16132-7 pubmed
    ..In assessing the four Ib-V-IX genes as a group, all four have a simple, "intron-depleted" structure with the entire open reading frame of the mature polypeptide located within a single exon.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  36. Ludlow L, Schick B, Budarf M, Driscoll D, Zackai E, Cohen A, et al. Identification of a mutation in a GATA binding site of the platelet glycoprotein Ibbeta promoter resulting in the Bernard-Soulier syndrome. J Biol Chem. 1996;271:22076-80 pubmed
  37. Suzuki K, Hayashi T, Yahagi A, Akiba J, Tajima K, Satoh S, et al. Novel point mutation in the leucine-rich motif of the platelet glycoprotein IX associated with Bernard-Soulier syndrome. Br J Haematol. 1997;99:794-800 pubmed
  38. Kenny D, Jonsson O, Morateck P, Montgomery R. Naturally occurring mutations in glycoprotein Ibalpha that result in defective ligand binding and synthesis of a truncated protein. Blood. 1998;92:175-83 pubmed
  39. Simon D, Chen Z, Xu H, Li C, Dong J, McIntire L, et al. Platelet glycoprotein ibalpha is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18). J Exp Med. 2000;192:193-204 pubmed
    ..These observations provide a molecular target for disrupting leukocyte-platelet complexes that promote vascular inflammation in thrombosis, atherosclerosis, and angioplasty-related restenosis. ..
  40. Kunishima S, Naoe T, Kamiya T, Saito H. Novel heterozygous missense mutation in the platelet glycoprotein Ib beta gene associated with isolated giant platelet disorder. Am J Hematol. 2001;68:249-55 pubmed
  41. Yap C, Anderson K, Hughan S, Dopheide S, Salem H, Jackson S. Essential role for phosphoinositide 3-kinase in shear-dependent signaling between platelet glycoprotein Ib/V/IX and integrin alpha(IIb)beta(3). Blood. 2002;99:151-8 pubmed
    ..Under static conditions, platelets appear to mobilize intracellular calcium through both PI 3-kinase-dependent and -independent mechanisms, whereas under shear PI 3-kinase is indispensable for VWF-induced calcium release. ..
  42. Strassel C, Pasquet J, Alessi M, Juhan Vague I, Chambost H, Combrie R, et al. A novel missense mutation shows that GPIbbeta has a dual role in controlling the processing and stability of the platelet GPIb-IX adhesion receptor. Biochemistry. 2003;42:4452-62 pubmed
    ..Thus, a single amino acid substitution in the extracellular domain of GPIbbeta can affect both the maturation of GPIbalpha and GPIX stability. GPIbbeta has a pivotal role in regulating GPIb-IX-V biosynthesis. ..
  43. Gonzalez Manchon C, Larrucea S, Pastor A, Butta N, Arias Salgado E, Ayuso M, et al. Compound heterozygosity of the GPIbalpha gene associated with Bernard-Soulier syndrome. Thromb Haemost. 2001;86:1385-91 pubmed
    ..Our findings indicate that the additive effects of both mutations are responsible for the BSS phenotype of the patients. ..
  44. Li Z, Xi X, Gu M, Feil R, Ye R, Eigenthaler M, et al. A stimulatory role for cGMP-dependent protein kinase in platelet activation. Cell. 2003;112:77-86 pubmed
    ..The cGMP-stimulated platelet responses are biphasic, consisting of an initial transient stimulatory response that promotes platelet aggregation and a subsequent inhibitory response that limits the size of thrombi. ..
  45. Englund G, Bodnar R, Li Z, Ruggeri Z, Du X. Regulation of von Willebrand factor binding to the platelet glycoprotein Ib-IX by a membrane skeleton-dependent inside-out signal. J Biol Chem. 2001;276:16952-9 pubmed
    ..CD also reverses the inhibitory effects of prostaglandin E1 on vWF binding to GPIb-IX. Thus, GPIb-IX-dependent platelet adhesion is doubly controlled by vWF conformation and a membrane skeleton-dependent inside-out signal. ..
  46. Vanhoorelbeke K, Schlammadinger A, Delville J, Handsaeme J, Vandecasteele G, Vauterin S, et al. Occurrence of the Asn45Ser mutation in the GPIX gene in a Belgian patient with Bernard Soulier syndrome. Platelets. 2001;12:114-20 pubmed
  47. Kunishima S, Tomiyama Y, Honda S, Kurata Y, Kamiya T, Ozawa K, et al. Cys97-->Tyr mutation in the glycoprotein IX gene associated with Bernard-Soulier syndrome. Br J Haematol. 1999;107:539-45 pubmed
    ..Transient transfection studies confirmed that mutant GPIX was not expressed on the transfected cells, showing that the mutation was responsible for the BSS phenotype observed in the patient. ..
  48. Noris P, Arbustini E, Spedini P, Belletti S, Balduini C. A new variant of Bernard-Soulier syndrome characterized by dysfunctional glycoprotein (GP) Ib and severely reduced amounts of GPIX and GPV. Br J Haematol. 1998;103:1004-13 pubmed
    ..Moreover, in one patient, normalization of bleeding time and rise of von Willebrand factor plasma concentration did not seem to be directly related. ..
  49. Ulsemer P, Strassel C, Baas M, Salamero J, Chasserot Golaz S, Cazenave J, et al. Biosynthesis and intracellular post-translational processing of normal and mutant platelet glycoprotein GPIb-IX. Biochem J. 2001;358:295-303 pubmed
    ..The present study has shown that transfer from the ER to the Golgi represents an important step for controlling post-translational processing and surface expression of normal GPIb-IX-V complex. ..
  50. Li Z, Xi X, Du X. A mitogen-activated protein kinase-dependent signaling pathway in the activation of platelet integrin alpha IIbbeta3. J Biol Chem. 2001;276:42226-32 pubmed
    ..Thus, our data delineate a novel integrin activation pathway in which ligand binding to GPIb-IX activates PKG that stimulates MAPK pathway, leading to integrin activation. ..
  51. Huang K, Ko T, Hung C, Chu J, Wang A, Chiou S. Crystal structure of a platelet-agglutinating factor isolated from the venom of Taiwan habu (Trimeresurus mucrosquamatus). Biochem J. 2004;378:399-407 pubmed publisher
    ..Conceivably, this interesting venom factor may provide a useful tool to study platelet agglutination by binding to the GPIb-IX-V complex...
  52. Morel O, Hugel B, Jesel L, Lanza F, Douchet M, Zupan M, et al. Sustained elevated amounts of circulating procoagulant membrane microparticles and soluble GPV after acute myocardial infarction in diabetes mellitus. Thromb Haemost. 2004;91:345-53 pubmed
    ..9 +/- 4.8 vs. 12.3 +/- 2.7 nM PhtdSer, p = 0.02), suggesting a prognostic potential for MP. ..
  53. Keuren J, Wielders S, Ulrichts H, Hackeng T, Heemskerk J, Deckmyn H, et al. Synergistic effect of thrombin on collagen-induced platelet procoagulant activity is mediated through protease-activated receptor-1. Arterioscler Thromb Vasc Biol. 2005;25:1499-505 pubmed
    ..The interaction of thrombin with PAR-1 mediates a synergistic effect on collagen-induced procoagulant activity by inducing a sustained elevation in [Ca2+]i in a subpopulation of platelets. ..