Genomes and Genes
Gene Symbol: integrin beta3
Description: integrin subunit beta 3
Alias: BDPLT16, BDPLT2, CD61, GP3A, GPIIIa, integrin beta-3, antigen CD61, integrin beta 3, integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61), platelet membrane glycoprotein IIIa
Products: integrin beta3
- Duan H, Cai Y, Sun X. Platelet glycoprotein IIb/IIIa polymorphism HPA-3 b/b is associated with increased risk of ischemic stroke in patients under 60 years of age. Med Sci Monit. 2012;18:CR19-24 pubmed..with stroke risk in 306 patients with acute ischemic stroke and 266 control subjects by determining the GpIIb and GpIIIa genotype from leukocyte DNA by polymerase chain reaction (PCR) followed by FokI and ScrFI digestion, respectively...
- Galasso G, Santulli G, Piscione F, De Rosa R, Trimarco V, Piccolo R, et al. The GPIIIA PlA2 polymorphism is associated with an increased risk of cardiovascular adverse events. BMC Cardiovasc Disord. 2010;10:41 pubmed publisher..39; Wald: 7.15; p = 0.001). Our study demonstrates that in patients with severe atherosclerosis the presence of PlA2 allele is associated with thrombotic cardiovascular complications. ..
- Aydinalp A, Atar I, Atac F, Yazici A, Cicek M, Yilmaz M, et al. Glycoprotein IIIa gene polymorphism and coronary artery disease. Acta Cardiol. 2010;65:225-30 pubmed..The glycoprotein IIb/IIIa genotype was not shown to indicate the presence of atherosclerotic plaque. There was no correlation between the genotype and plaque vulnerability. ..
- Fujita M, Takada Y, Takada Y. Integrins ?v?3 and ?4?1 act as coreceptors for fractalkine, and the integrin-binding defective mutant of fractalkine is an antagonist of CX3CR1. J Immunol. 2012;189:5809-19 pubmed publisher..These findings suggest that K36E/R37E acts as a dominant-negative CX3CR1 antagonist and that FKN-CD/integrin interaction is a novel therapeutic target in inflammatory diseases. ..
- Lau T, Kim C, Ginsberg M, Ulmer T. The structure of the integrin alphaIIbbeta3 transmembrane complex explains integrin transmembrane signalling. EMBO J. 2009;28:1351-61 pubmed publisher..The structurally unique, highly conserved integrin alphaIIbbeta3 TM complex rationalizes bi-directional signalling and represents the first structure of a heterodimeric TM receptor complex. ..
- Ashavaid T, Todur S, Kondkar A, Nair K, Shalia K, Dalal J, et al. Platelet polymorphisms: frequency distribution and association with coronary artery disease in an Indian population. Platelets. 2011;22:85-91 pubmed publisher..This is the first study to evaluate the role of gene polymorphisms in both the thrombotic and fibrinolytic pathway in the Indian population and suggests that tPA I/D polymorphism confers CAD risk in our population. ..
- Gong H, Shen B, Flevaris P, Chow C, Lam S, Voyno Yasenetskaya T, et al. G protein subunit Galpha13 binds to integrin alphaIIbbeta3 and mediates integrin "outside-in" signaling. Science. 2010;327:340-3 pubmed publisher..We found that the heterotrimeric guanine nucleotide-binding protein (G protein) Galpha13 directly bound to the integrin beta3 cytoplasmic domain and that Galpha13-integrin interaction was promoted by ligand binding to the integrin ..
- Lorger M, Krueger J, O Neal M, Staflin K, Felding Habermann B. Activation of tumor cell integrin alphavbeta3 controls angiogenesis and metastatic growth in the brain. Proc Natl Acad Sci U S A. 2009;106:10666-71 pubmed publisher..Targeting this molecular mechanism could prove valuable for the inhibition of brain metastasis. ..
- Santiago Germán D, Leaños Miranda A, Garcia Latorre E, Borrayo Sánchez G, Majluf Cruz A, Isordia Salas I. Platelet glycoprotein IIIA PIA2 polymorphism is associated with ST elevation acute myocardial infarction in young Mexican population. J Thromb Thrombolysis. 2012;33:389-96 pubmed publisher..study was to determine the frequency distribution and association of polymorphism in the platelet glycoprotein GPIIIa PLA/A2 and the possible interaction with the 4G/5G in the plasminogen activator inhibitor genes with ST elevation ..
- Var A, Utuk O, Akcali S, Sanlidag T, Uyanik B, Dinc G. Impact of hemostatic gene single point mutations in patients with non-diabetic coronary artery disease. Mol Biol Rep. 2009;36:2235-43 pubmed publisher..However, lower frequency of FXIII Val34Leu and MTHFR C677T polymorphisms may decrease, while FV Leiden polymorphism may increase development of nDCAD. ..
- Gaillard T, Dejaegere A, Stote R. Dynamics of beta3 integrin I-like and hybrid domains: insight from simulations on the mechanism of transition between open and closed forms. Proteins. 2009;76:977-94 pubmed publisher..From our results, we propose that these two helices function in tandem to initiate large-scale, interdomain conformational transition apparent in integrin activation and signaling. ..
- Seguin L, Kato S, Franovic A, Camargo M, Lesperance J, Elliott K, et al. An integrin Î²â‚ƒ-KRAS-RalB complex drives tumour stemness and resistance to EGFR inhibition. Nat Cell Biol. 2014;16:457-68 pubmed publisher..These findings not only identify Î±(v)Î²â‚ƒ as a marker/driver of carcinoma stemness but also reveal a therapeutic strategy to sensitize such tumours to RTK inhibition. ..
- Luo B, Karanicolas J, Harmacek L, Baker D, Springer T. Rationally designed integrin beta3 mutants stabilized in the high affinity conformation. J Biol Chem. 2009;284:3917-24 pubmed publisher..This detailed understanding of the conformational change will assist in the development of allosteric drugs that either stabilize or destabilize specific integrin conformations without occluding the ligand-binding site. ..
- Perera H, Ma Y, Yang J, HIRBAWI J, Plow E, Qin J. Membrane binding of the N-terminal ubiquitin-like domain of kindlin-2 is crucial for its regulation of integrin activation. Structure. 2011;19:1664-71 pubmed publisher..These data suggest a membrane-binding function of the ubiquitin-like domain of kindlin-2, which is likely common for all kindlins to promote their localization to the plasma membrane and control integrin activation. ..
- Somanath P, Malinin N, Byzova T. Cooperation between integrin alphavbeta3 and VEGFR2 in angiogenesis. Angiogenesis. 2009;12:177-85 pubmed publisher..The pathological consequences and regulatory events involved in this receptor cross-talk are also presented. ..
- Oxboel J, Binderup T, Knigge U, Kjaer A. Quantitative gene-expression of the tumor angiogenesis markers vascular endothelial growth factor, integrin alphaV and integrin beta3 in human neuroendocrine tumors. Oncol Rep. 2009;21:769-75 pubmed..PCR for measuring mRNA gene-expression of vascular endothelial growth factor (VEGF), integrin alphaV, and integrin beta3, and CD34 for a group of patients with neuroendocrine tumors (n=13)...
- Chen Y, Wei Y, Chen H, Fong Y, Hsu C, Tsai C, et al. Osteopontin increases migration and MMP-9 up-regulation via alphavbeta3 integrin, FAK, ERK, and NF-kappaB-dependent pathway in human chondrosarcoma cells. J Cell Physiol. 2009;221:98-108 pubmed publisher..Taken together, our results indicated that OPN enhances the migration of chondrosarcoma cells by increasing MMP-9 expression through the alphavbeta3 integrin, FAK, MEK, ERK and NF-kappaB signal transduction pathway. ..
- Syros G, Mehran R, Weisz G, Kittas C, Moses J, Leon M, et al. Role of PLA2 polymorphism on clinical events after percutaneous coronary intervention. Acute Card Care. 2009;11:88-91 pubmed publisherWe examined the relationship between the PLA2 polymorphism of the platelet GPIIIa receptor and major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI)...
- Simon T, Verstuyft C, Mary Krause M, Quteineh L, Drouet E, Meneveau N, et al. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med. 2009;360:363-75 pubmed publisher..This effect was particularly marked among the patients undergoing percutaneous coronary intervention. (ClinicalTrials.gov number, NCT00673036.) ..
- Abboud N, Ghazouani L, Ben Hadj Khalifa S, Anabi F, Added F, Khalfallah A, et al. Human platelet alloantigens HPA-1, HPA-2, and HPA-3 polymorphisms associated with extent of severe coronary artery disease. J Thromb Thrombolysis. 2010;29:409-15 pubmed publisher..49; 95% CI = 1.06-5.86) to be positively associated with CAD, after adjusting for a number of covariates. Our results demonstrate positive association of HPA variants and specific HPA-1/HPA-2/HPA-3 haplotypes with CAD in Tunisians. ..
- Blue R, Li J, Steinberger J, Murcia M, Filizola M, Coller B. Effects of limiting extension at the alphaIIb genu on ligand binding to integrin alphaIIbbeta3. J Biol Chem. 2010;285:17604-13 pubmed publisher..Our data are consistent with alphaIIb extension resulting in increased access to the ligand-binding site and/or facilitating the conformational change(s) in beta3 that affect the intrinsic affinity of the binding pocket for ligand. ..
- Raborn J, Luo B. Mutagenesis studies of the ? I domain metal ion binding sites on integrin ?V?3 ligand binding affinity. J Cell Biochem. 2012;113:1190-7 pubmed publisher..Our study suggests that the variation of this residue contributes to the different ligand binding affinities and adhesion abilities among different integrin families. ..
- Desgrosellier J, Lesperance J, Seguin L, Gozo M, Kato S, Franovic A, et al. Integrin Î±vÎ²3 drives slug activation and stemness in the pregnant and neoplastic mammary gland. Dev Cell. 2014;30:295-308 pubmed publisher..Thus, pregnancy-associated MaSCs require a TGF-Î²2/Î±vÎ²3/Slug pathway, which may contribute to breast cancer progression and stemness. ..
- Liu L, Craig A, Meldrum H, Marcovina S, Elliott B, Koschinsky M. Apolipoprotein(a) stimulates vascular endothelial cell growth and migration and signals through integrin alphaVbeta3. Biochem J. 2009;418:325-36 pubmed publisher..Taken together, the results of the present study suggest that the apo(a) component of Lp(a) signals through integrin alphaVbeta3 to activate endothelial cells. ..
- Litvinov R, Barsegov V, Schissler A, Fisher A, Bennett J, Weisel J, et al. Dissociation of bimolecular ?IIb?3-fibrinogen complex under a constant tensile force. Biophys J. 2011;100:165-73 pubmed publisher..Taken together, these data provide important quantitative and qualitative characteristics of ?IIb?3-fibrinogen binding and unbinding that underlie the dynamics of platelet adhesion and aggregation in blood flow. ..
- Xu B, Sun X, Li L, Wu L, Zhang A, Feng Y. Pinopodes, leukemia inhibitory factor, integrin-?3, and mucin-1 expression in the peri-implantation endometrium of women with unexplained recurrent pregnancy loss. Fertil Steril. 2012;98:389-95 pubmed publisher..The morphology and the coverage of pinopodes and expression of LIF and integrin-?3 did not change, but MUC1 expression was statistically significantly reduced in women with RPL compared with normal women. ..
- Pavlova T, Poliakov V, Dupliakov D, Khokhlunov S, Kirillov V, Shavkunov S. [Distributions of polymorphisms of genes of some components of hemostasis in patients with ischemic heart disease]. Kardiologiia. 2009;49:9-13 pubmedWe have studied structure of polymorphisms of genes of blood clotting factors II, V, VII, platelet membrane glycoprotein IIIa (GPIIIa) and enzyme methylenetetrahydrofolate reductase (MTHFR) in patients with ischemic heart disease (IHD)...
- Mikelis C, Sfaelou E, Koutsioumpa M, Kieffer N, Papadimitriou E. Integrin alpha(v)beta(3) is a pleiotrophin receptor required for pleiotrophin-induced endothelial cell migration through receptor protein tyrosine phosphatase beta/zeta. FASEB J. 2009;23:1459-69 pubmed publisher..Collectively, these data suggest that alpha(nu)beta(3) is a key molecule that determines the stimulatory or inhibitory effect of PTN on cell migration. ..
- Abboud N, Amin H, Ghazouani L, Ben Haj Khalifa S, Ben Khalafallah A, Aded F, et al. Polymorphisms of human platelet alloantigens HPA-1 and HPA-2 associated with severe coronary artery disease. Cardiovasc Pathol. 2010;19:302-7 pubmed publisher..92; 95% CI=1.43-5.94) haplotypes with CAD, after adjustment for a number of covariates. Our results suggest that HPA-1/HPA-2 haplotypes may be considered to be a major risk factor for CAD in middle-aged Tunisians. ..
- Bledzka K, Bialkowska K, Nie H, Qin J, Byzova T, Wu C, et al. Tyrosine phosphorylation of integrin beta3 regulates kindlin-2 binding and integrin activation. J Biol Chem. 2010;285:30370-4 pubmed publisher..These observations indicate that transitions between the phosphorylated and non-phosphorylated states of the integrin ?(3) CT determine reactivity with kindlin-2 and govern the role of kindlin-2 in regulating integrin activation. ..
- Kunicki T, Williams S, Nugent D, Harrison P, Segal H, Syed A, et al. Lack of association between aspirin responsiveness and seven candidate gene haplotypes in patients with symptomatic vascular disease. Thromb Haemost. 2009;101:123-33 pubmed..03) and plasma von Willebrand Factor antigen levels (p < 0.001), which likely contributes to resistance to the inhibitory effects of ASA in the PFA-100. ..
- Lössner D, Abou Ajram C, Benge A, Aumercier M, Schmitt M, Reuning U. Integrin alphavbeta3 upregulates integrin-linked kinase expression in human ovarian cancer cells via enhancement of ILK gene transcription. J Cell Physiol. 2009;220:367-75 pubmed publisher..By increasing ILK as an important integrin-proximal kinase, alphavbeta3 may promote its intracellular signaling and tumor biological processes arising thereof in favor of ovarian cancer metastasis. ..
- Kunicki T, Williams S, Nugent D, Yeager M. Mean platelet volume and integrin alleles correlate with levels of integrins ?(IIb)?(3) and ?(2)?(1) in acute coronary syndrome patients and normal subjects. Arterioscler Thromb Vasc Biol. 2012;32:147-52 pubmed publisher..Because of the hyperactivity of larger platelets, MPV is an accurate metric of risk for adverse outcome in ACS. ..
- Alghisi G, Ponsonnet L, Ruegg C. The integrin antagonist cilengitide activates alphaVbeta3, disrupts VE-cadherin localization at cell junctions and enhances permeability in endothelial cells. PLoS ONE. 2009;4:e4449 pubmed publisher..These effects are potentially relevant to the clinical use of cilengitide as anticancer agent. ..
- Maguire J, Thakkinstian A, Levi C, Lincz L, Bisset L, Sturm J, et al. Impact of COX-2 rs5275 and rs20417 and GPIIIa rs5918 polymorphisms on 90-day ischemic stroke functional outcome: a novel finding. J Stroke Cerebrovasc Dis. 2011;20:134-44 pubmed publisher..and genotyped for polymorphisms in platelet glycoprotein Ib? (GPIb?) rs224309 and rs6065, glycoprotein IIIa (GPIIIa) rs5918, tissue plasminogen activator (tPA) rs63020761, plasminogen activating inhibitor (PAI-1) rs72578597, and ..
- Malinin N, Zhang L, Choi J, Ciocea A, Razorenova O, Ma Y, et al. A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans. Nat Med. 2009;15:313-8 pubmed publisher..Furthermore, allogeneic bone marrow transplantation was shown to alleviate the symptoms of the disease. ..
- Cayla G, Hulot J, O Connor S, Pathak A, Scott S, Gruel Y, et al. Clinical, angiographic, and genetic factors associated with early coronary stent thrombosis. JAMA. 2011;306:1765-74 pubmed publisher..Future studies are needed to validate the prognostic accuracy of these risk factors in prospective cohorts. ..
- Hauschner H, Landau M, Seligsohn U, Rosenberg N. A unique interaction between alphaIIb and beta3 in the head region is essential for outside-in signaling-related functions of alphaIIbbeta3 integrin. Blood. 2010;115:4542-50 pubmed publisher..Together, these findings indicate that the interaction between Trp110 of alphaIIb and Arg261 of beta3 is critical for alphaIIbbeta3 integrity and outside-in signaling-related functions. ..
- Pellitero S, Reverter J, Tassies D, Pizarro E, Monteagudo J, Salinas I, et al. Polymorphisms in platelet glycoproteins Ia and IIIa are associated with arterial thrombosis and carotid atherosclerosis in type 2 diabetes. Thromb Haemost. 2010;103:630-7 pubmed publisher..42; p=0.04). In conclusion, the 807T allele of GP Ia and the PlA2 allele of GP IIIa, and specially its combination, may confer an additional risk for development of carotid atherosclerosis and arterial thrombosis in type 2 diabetes. ..
- Eng E, Smagghe B, Walz T, Springer T. Intact alphaIIbbeta3 integrin is extended after activation as measured by solution X-ray scattering and electron microscopy. J Biol Chem. 2011;286:35218-26 pubmed publisher..The observed extension and conformational rearrangement upon activation are consistent with the extension and headpiece opening model of integrin activation. ..
- Peck G, Smeeth L, Whittaker J, Casas J, Hingorani A, Sharma P. The genetics of primary haemorrhagic stroke, subarachnoid haemorrhage and ruptured intracranial aneurysms in adults. PLoS ONE. 2008;3:e3691 pubmed publisher..Importantly, for several alleles previously found to be associated with protection from ischaemic stroke, there was a trend towards an increased risk of haemorrhagic stroke. ..
- Qu H, Tu Y, Shi X, Larjava H, Saleem M, Shattil S, et al. Kindlin-2 regulates podocyte adhesion and fibronectin matrix deposition through interactions with phosphoinositides and integrins. J Cell Sci. 2011;124:879-91 pubmed publisher..Our results reveal important functions of kindlin-2 in the regulation of podocyte-matrix adhesion and matrix deposition and shed new light on the mechanism whereby kindlin-2 functions in these processes. ..
- Kucharska Newton A, Monda K, Campbell S, Bradshaw P, Wagenknecht L, Boerwinkle E, et al. Association of the platelet GPIIb/IIIa polymorphism with atherosclerotic plaque morphology: the Atherosclerosis Risk in Communities (ARIC) Study. Atherosclerosis. 2011;216:151-6 pubmed publisher..We examined the association of a single nucleotide polymorphism (SNP) in the GPIIIa platelet glycoprotein (Leu33Pro) with carotid artery plaque morphology and with expression of platelet markers ..
- Sudhakar A, Sugimoto H, Yang C, Lively J, Zeisberg M, Kalluri R. Human tumstatin and human endostatin exhibit distinct antiangiogenic activities mediated by alpha v beta 3 and alpha 5 beta 1 integrins. Proc Natl Acad Sci U S A. 2003;100:4766-71 pubmed..Collectively, such distinct properties of human tumstatin and human endostatin provide the first insight into their diverse antiangiogenic actions and argue for combining them for targeting tumor angiogenesis. ..
- Wegener K, Partridge A, Han J, Pickford A, Liddington R, Ginsberg M, et al. Structural basis of integrin activation by talin. Cell. 2007;128:171-82 pubmed..Here we define the structure of a complex between talin and the membrane-proximal integrin beta3 cytoplasmic domain and identify specific contacts between talin and the integrin tail required for activation...
- Chudakova D, Minushkina L, Zateishchikov D, Nosikov V. [Association of polymorphic marker A1/A2 of gene ITGB3 with coronary artery disease and myocardial infarction]. Genetika. 2004;40:1402-5 pubmed..This indicates that this polymorphic marker is not associated with either CAD or MI in the Moscow population. ..
- Gerold G, Abu Ajaj K, Bienert M, Laws H, Zychlinsky A, de Diego J. A Toll-like receptor 2-integrin beta3 complex senses bacterial lipopeptides via vitronectin. Nat Immunol. 2008;9:761-8 pubmed publisher..Notably, vitronectin and integrin beta(3) coordinated responses to other TLR2 agonists such as lipoteichoic acid and zymosan. Our findings show that vitronectin and integrin beta(3) contribute to the initiation of TLR2 responses. ..
- Jackson D, White M, Jennings L, Newman P. A Ser162-->Leu mutation within glycoprotein (GP) IIIa (integrin beta3) results in an unstable alphaIIbbeta3 complex that retains partial function in a novel form of type II Glanzmann thrombasthenia. Thromb Haemost. 1998;80:42-8 pubmed..Taken together, these data implicate the region encompassing Ser162 in the stabilization and ligand binding properties of the alphaIIbbeta3 complex. ..
- Castro V, Alberto F, Costa R, Lepikson Neto J, Gualandro S, Figueiredo M, et al. Polymorphism of the human platelet antigen-5 system is a risk factor for occlusive vascular complications in patients with sickle cell anemia. Vox Sang. 2004;87:118-23 pubmed..The findings of this study suggest that the HPA-5b allele is a genetic risk factor for the development of OVC in patients with SCA. This allele could be explored as a target for the development of new therapeutic approaches. ..
- Slowik A, Dziedzic T, Turaj W, Pera J, Glodzik Sobanska L, Szermer P, et al. A2 alelle of GpIIIa gene is a risk factor for stroke caused by large-vessel disease in males. Stroke. 2004;35:1589-93 pubmedGlycoprotein IIIa (GpIIIa) is a platelet membrane receptor for fibrinogen and von Willebrand factor. It plays a key role in platelet aggregation...
- Iniesta J, Corral J, Gonzalez Conejero R, Piqueras C, Vicente V. Polymorphisms of platelet adhesive receptors: do they play a role in primary intracerebral hemorrhage?. Cerebrovasc Dis. 2003;15:51-5 pubmed..The frequency of genotypes and alleles were similar between patients and controls. Our results suggest that these polymorphisms play a minor role in PIH. ..
- Obergfell A, Eto K, Mocsai A, Buensuceso C, Moores S, Brugge J, et al. Coordinate interactions of Csk, Src, and Syk kinases with [alpha]IIb[beta]3 initiate integrin signaling to the cytoskeleton. J Cell Biol. 2002;157:265-75 pubmed..These studies establish that platelet spreading on fibrinogen requires sequential activation of Src and Syk in proximity to alphaIIbbeta3, thus providing a paradigm for initiation of integrin signaling to the actin cytoskeleton. ..
- Zhu J, Carman C, Kim M, Shimaoka M, Springer T, Luo B. Requirement of alpha and beta subunit transmembrane helix separation for integrin outside-in signaling. Blood. 2007;110:2475-83 pubmed..This defect was rescued by reduction of the disulfide bond. Our results demonstrate that the separation of transmembrane domains is required for integrin outside-in signal transduction. ..