Genomes and Genes
Gene Symbol: Itga2b
Description: integrin alpha 2b
Alias: AI172977, CD41, CD41B, GpIIb, alphaIIb, integrin alpha-IIb, GP IIb, GPalpha IIb, alpha IIb, platelet glycoprotein IIb of IIb/II Ia complex, platelet membrane glycoprotein IIb
- Emambokus N, Frampton J. The glycoprotein IIb molecule is expressed on early murine hematopoietic progenitors and regulates their numbers in sites of hematopoiesis. Immunity. 2003;19:33-45 pubmedThe alpha integrin GPIIb is a marker of hematopoietic progenitors...
- Swiers G, Baumann C, O Rourke J, Giannoulatou E, Taylor S, Joshi A, et al. Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level. Nat Commun. 2013;4:2924 pubmed publisher..Our data therefore provide important insights on the timeline of early haematopoietic commitment. ..
- Mikkola H, Fujiwara Y, Schlaeger T, Traver D, Orkin S. Expression of CD41 marks the initiation of definitive hematopoiesis in the mouse embryo. Blood. 2003;101:508-16 pubmed..cell fate, we compared wild-type and SCL(-/-) embryonic stem cell differentiation in vitro and identified CD41 (GpIIb) as the earliest surface marker missing from SCL(-/-) embryoid bodies (EBs)...
- Schultz J, Mayernik L, Rout U, Armant D. Integrin trafficking regulates adhesion to fibronectin during differentiation of mouse peri-implantation blastocysts. Dev Genet. 1997;21:31-43 pubmed..Trafficking of alpha 5 beta 1, and possibly other integrins, to the apical surface of trophoblast cells appears to be a critical step in the differentiation of the mouse blastocyst to an invasive phenotype. ..
- Wilson N, Foster S, Wang X, Knezevic K, Schütte J, Kaimakis P, et al. Combinatorial transcriptional control in blood stem/progenitor cells: genome-wide analysis of ten major transcriptional regulators. Cell Stem Cell. 2010;7:532-44 pubmed publisher..Taken together, this study demonstrates the power of genome-wide analysis in generating novel functional insights into the transcriptional control of stem and progenitor cells. ..
- Gushiken F, Patel V, Liu Y, Pradhan S, Bergeron A, Peng Y, et al. Protein phosphatase 2A negatively regulates integrin alpha(IIb)beta(3) signaling. J Biol Chem. 2008;283:12862-9 pubmed publisher..These studies demonstrate that PP2Ac (alpha) can negatively regulate integrin alpha(IIb)beta(3) signaling by suppressing the ERK1/2 signaling pathway. ..
- Petrich B, Marchese P, Ruggeri Z, Spiess S, Weichert R, Ye F, et al. Talin is required for integrin-mediated platelet function in hemostasis and thrombosis. J Exp Med. 2007;204:3103-11 pubmed..These data establish that platelet talin plays a crucial role in hemostasis and provide the first proof that talin is required for the activation and function of mammalian alpha2beta1 and alphaIIbbeta3 integrins in vivo. ..
- Zhang J, Varas F, Stadtfeld M, Heck S, Faust N, Graf T. CD41-YFP mice allow in vivo labeling of megakaryocytic cells and reveal a subset of platelets hyperreactive to thrombin stimulation. Exp Hematol. 2007;35:490-499 pubmedDevelopment of a mouse line permitting live imaging of cells expressing CD41/GpIIb as a means to study megakaryopoiesis...
- Kaiser W, Upton J, Long A, Livingston Rosanoff D, Daley Bauer L, Hakem R, et al. RIP3 mediates the embryonic lethality of caspase-8-deficient mice. Nature. 2011;471:368-72 pubmed publisher..Thus, Casp8 contributes to homeostatic control in the adult immune system; however, RIP3 and Casp8 are together completely dispensable for mammalian development. ..
- Rolny C, Nilsson I, Magnusson P, Armulik A, Jakobsson L, Wentzel P, et al. Platelet-derived growth factor receptor-beta promotes early endothelial cell differentiation. Blood. 2006;108:1877-86 pubmed..precursors express PDGFR-beta based on coexpression with CD31, vascular endothelial growth factor receptor-2, and CD41 in 2 models: mouse yolk sac (embryonic day 8 [E8]) and differentiating mouse embryonic stem cells (embryoid bodies)...
- Chen J, Tan K, Zhou H, Lo H, Tronik Le Roux D, Liddington R, et al. Modifying murine von Willebrand factor A1 domain for in vivo assessment of human platelet therapies. Nat Biotechnol. 2008;26:114-9 pubmed..Thus, by modifying a protein interface, we have generated a potential biological platform for preclinical screening of antithrombotics that specifically target human platelets. ..
- Gaertner F, Ahmad Z, Rosenberger G, Fan S, Nicolai L, Busch B, et al. Migrating Platelets Are Mechano-scavengers that Collect and Bundle Bacteria. Cell. 2017;171:1368-1382.e23 pubmed publisher..This assigns platelets a central role in innate immune responses and identifies them as potential targets to dampen inflammatory tissue damage in clinical scenarios of severe systemic infection. ..
- 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. ..
- Puzon McLaughlin W, Kamata T, Takada Y. Multiple discontinuous ligand-mimetic antibody binding sites define a ligand binding pocket in integrin alpha(IIb)beta(3). J Biol Chem. 2000;275:7795-802 pubmed..These results suggest that ligand-mimetic antibodies and probably native ligands may make direct contact with these discontinuous binding sites in both subunits, which may constitute a ligand-binding pocket. ..
- Stefanini L, Ye F, Snider A, Sarabakhsh K, Piatt R, Paul D, et al. A talin mutant that impairs talin-integrin binding in platelets decelerates ?IIb?3 activation without pathological bleeding. Blood. 2014;123:2722-31 pubmed publisher..Together our data indicate that reduction of talin-?3 integrin binding affinity results in decelerated ?IIb?3 integrin activation and protection from arterial thrombosis without pathological bleeding. ..
- Nishimura S, Manabe I, Nagasaki M, Kakuta S, Iwakura Y, Takayama N, et al. In vivo imaging visualizes discoid platelet aggregations without endothelium disruption and implicates contribution of inflammatory cytokine and integrin signaling. Blood. 2012;119:e45-56 pubmed publisher..Actin linker talin-dependent activation of alphaIIb-beta3 integrin or Rac1 in platelets was required for late-phase thrombus stability...
- Dicker I, Pedicord D, Seiffert D, Jamieson G, Greco N. Both the high affinity thrombin receptor (GPIb-IX-V) and GPIIb/IIIa are implicated in expression of thrombin-induced platelet procoagulant activity. Thromb Haemost. 2001;86:1065-9 pubmed..abrogated in the presence of a combination of both LJIb10 and c7E3, a MoAb directed against alphaIIbbeta3 (GPIIb/IIIa). In contrast...
- Kiyomizu K, Kashiwagi H, Nakazawa T, Tadokoro S, Honda S, Kanakura Y, et al. Recognition of highly restricted regions in the ?-propeller domain of ?IIb by platelet-associated anti-?IIb?3 autoantibodies in primary immune thrombocytopenia. Blood. 2012;120:1499-509 pubmed publisher..Of 11 eluates whose recognition sites were identified, 5 clearly showed restricted ?/?-chain usage. These results suggested that PA anti-?IIb?3 Abs in primary ITP tended to recognize highly restricted regions of ?IIb with clonality. ..
- Wong C, Jenne C, Petri B, Chrobok N, Kubes P. Nucleation of platelets with blood-borne pathogens on Kupffer cells precedes other innate immunity and contributes to bacterial clearance. Nat Immunol. 2013;14:785-92 pubmed publisher..MRSA) were rapidly caught by KCs and triggered platelets to switch from 'touch-and-go' adhesion to sustained GPIIb-mediated adhesion on the KC surface to encase the bacterium...
- Zimdahl H, Kreitler T, Gosele C, Ganten D, Hubner N. Conserved synteny in rat and mouse for a blood pressure QTL on human chromosome 17. Hypertension. 2002;39:1050-2 pubmed..The critical segment on human chromosome 17 spans a large interval containing the genes Itga2b, Gfap, and Itgb3...
- Thornton M, Zhang C, Kowalska M, Poncz M. Identification of distal regulatory regions in the human alpha IIb gene locus necessary for consistent, high-level megakaryocyte expression. Blood. 2002;100:3588-96 pubmedThe alphaIIb/beta3-integrin receptor is present at high levels only in megakaryocytes and platelets. Its presence on platelets is critical for hemostasis...
- Ray A, Treloar H. IgSF8: a developmentally and functionally regulated cell adhesion molecule in olfactory sensory neuron axons and synapses. Mol Cell Neurosci. 2012;50:238-49 pubmed publisher..These data support the hypothesis that IgSF8 facilitates OSN synapse formation. ..
- Goldie L, Lucitti J, Dickinson M, Hirschi K. Cell signaling directing the formation and function of hemogenic endothelium during murine embryogenesis. Blood. 2008;112:3194-204 pubmed publisher..Thus, we identify a novel, critical role for RA signaling in the development of hemogenic endothelium that contributes to definitive hematopoiesis. ..
- Kasirer Friede A, Kang J, Kahner B, Ye F, Ginsberg M, Shattil S. ADAP interactions with talin and kindlin promote platelet integrin Î±IIbÎ²3 activation and stable fibrinogen binding. Blood. 2014;123:3156-65 pubmed publisher..Thus, ADAP uniquely promotes activation of and irreversible fibrinogen binding to platelet Î±IIbÎ²3 through interactions with talin and kindlin-3. ..
- Schoenwaelder S, Ono A, Nesbitt W, Lim J, Jarman K, Jackson S. Phosphoinositide 3-kinase p110 beta regulates integrin alpha IIb beta 3 avidity and the cellular transmission of contractile forces. J Biol Chem. 2010;285:2886-96 pubmed publisher..These findings may provide new insight into the potential antithrombotic properties of PI3K p110 beta inhibitors. ..
- García P, Clarke M, Vegiopoulos A, Berlanga O, Camelo A, Lorvellec M, et al. Reduced c-Myb activity compromises HSCs and leads to a myeloproliferation with a novel stem cell basis. EMBO J. 2009;28:1492-504 pubmed publisher..Instead, cells positive for Kit and expressing low to medium levels of CD11b acquire self-renewing stem cell properties and are responsible for the perpetuation of the myeloproliferative phenotype. ..
- Hart A, Melet F, Grossfeld P, Chien K, Jones C, Tunnacliffe A, et al. Fli-1 is required for murine vascular and megakaryocytic development and is hemizygously deleted in patients with thrombocytopenia. Immunity. 2000;13:167-77 pubmed..We map the megakaryocytic defects in 14 Jacobsen patients to a minimal region on 11q that includes the Fli-1 gene and suggest that dysmegakaryopoiesis in these patients may be caused by hemizygous loss of Fli-1. ..
- Nieswandt B, Schulte V, Zywietz A, Gratacap M, Offermanns S. Costimulation of Gi- and G12/G13-mediated signaling pathways induces integrin alpha IIbbeta 3 activation in platelets. J Biol Chem. 2002;277:39493-8 pubmed
- Goschnick M, Lau L, Wee J, Liu Y, Hogarth P, Robb L, et al. Impaired "outside-in" integrin alphaIIbbeta3 signaling and thrombus stability in TSSC6-deficient mice. Blood. 2006;108:1911-8 pubmed..These data demonstrate that TSSC6 appears to regulate integrin alpha(IIb)beta(3) "outside-in" signaling events in platelets and is necessary for stability of arterial thrombi in vivo. ..
- Cordeiro O, Chypre M, Brouard N, Rauber S, Alloush F, Romera Hernandez M, et al. Integrin-Alpha IIb Identifies Murine Lymph Node Lymphatic Endothelial Cells Responsive to RANKL. PLoS ONE. 2016;11:e0151848 pubmed publisher..Here we show that integrin alpha 2b (ITGA2b), known to be carried by platelets, megakaryocytes and hematopoietic progenitors, is expressed by a lymph node ..
- Braun A, Bordoy R, Stanchi F, Moser M, Kostka G G, Ehler E, et al. PINCH2 is a new five LIM domain protein, homologous to PINCHand localized to focal adhesions. Exp Cell Res. 2003;284:239-50 pubmed..Finally, we demonstrate that PINCH2 localizes to focal adhesions in NIH 3T3 cells and to Z-disks in primary rat cardiomyocytes. ..
- Mattheij N, Gilio K, van Kruchten R, Jobe S, Wieschhaus A, Chishti A, et al. Dual mechanism of integrin ?IIb?3 closure in procoagulant platelets. J Biol Chem. 2013;288:13325-36 pubmed publisher..Inactivation of integrin ?IIb?3 reverses platelet aggregate formation upon coagulation...
- Oki T, Kitaura J, Eto K, Lu Y, Maeda Yamamoto M, Inagaki N, et al. Integrin alphaIIbbeta3 induces the adhesion and activation of mast cells through interaction with fibrinogen. J Immunol. 2006;176:52-60 pubmedIntegrin alphaIIb, a well-known marker of megakaryocyte-platelet lineage, has been recently recognized on hemopoietic progenitors...
- Lee L, Ghorbanian Y, Wang W, Wang Y, Kim Y, Weissman I, et al. LYVE1 Marks the Divergence of Yolk Sac Definitive Hemogenic Endothelium from the Primitive Erythroid Lineage. Cell Rep. 2016;17:2286-2298 pubmed publisher..Lyve1-Cre thus marks the divergence between YS primitive and definitive hematopoiesis and provides a tool for targeting YS definitive hematopoiesis and FL colonization. ..
- Shimizu R, Kobayashi E, Engel J, Yamamoto M. Induction of hyperproliferative fetal megakaryopoiesis by an N-terminally truncated GATA1 mutant. Genes Cells. 2009;14:1119-31 pubmed publisher..This mouse model serves as an important means to clarify how impaired GATA1 function contributes to the multi-step leukemogenesis. ..
- Gushiken F, Hyojeong H, Pradhan S, Langlois K, Alrehani N, Cruz M, et al. The catalytic subunit of protein phosphatase 1 gamma regulates thrombin-induced murine platelet alpha(IIb)beta(3) function. PLoS ONE. 2009;4:e8304 pubmed publisher..These studies illustrate a role for PP1cgamma in maintaining GSK3beta-serine9 phosphorylation downstream of thrombin signaling and promoting thrombus formation via fibrinogen binding and platelet aggregation. ..
- Mayanglambam A, Bhavanasi D, Vijayan K, Kunapuli S. Differential dephosphorylation of the protein kinase C-zeta (PKC?) in an integrin ?IIb?3-dependent manner in platelets. Biochem Pharmacol. 2011;82:505-13 pubmed publisher..This differential dephosphorylation of PKC? might be an important regulatory mechanism for platelet functional responses. ..
- Reddy K, Smith D, Plow E. Analysis of Fyn function in hemostasis and alphaIIbbeta3-integrin signaling. J Cell Sci. 2008;121:1641-8 pubmed publisher..Our results suggest that Fyn and Src have distinct requirements for interaction with alphaIIbbeta3; and, consequently, the two SFK can mediate different functional responses. ..
- Cho J, Degen J, Coller B, Mosher D. Fibrin but not adsorbed fibrinogen supports fibronectin assembly by spread platelets. Effects of the interaction of alphaIIb beta3 with the C terminus of the fibrinogen gamma-chain. J Biol Chem. 2005;280:35490-8 pubmed..Antibody and peptide blocking studies demonstrated that alphaIIb beta3 integrin mediates platelet adhesion to fibrinogen, whereas both alphav beta3 and alphaIIb beta3 mediate ..
- Azcoitia V, Aracil M, Martinez A C, Torres M. The homeodomain protein Meis1 is essential for definitive hematopoiesis and vascular patterning in the mouse embryo. Dev Biol. 2005;280:307-20 pubmed..Meis1 mutant mice also displayed complete agenesis of the megakaryocyte lineage and localized defects in vascular patterning, which may cause the hemorrhagic phenotype. ..
- Wang L, Wu Y, Zhou J, Ahmad S, Mutus B, Garbi N, et al. Platelet-derived ERp57 mediates platelet incorporation into a growing thrombus by regulation of the ?IIb?3 integrin. Blood. 2013;122:3642-50 pubmed publisher..In conclusion, platelet-derived ERp57 directly interacts with ?IIb?3 during activation of this receptor and is required for incorporation of platelets into a growing thrombus. ..
- Levi B, Yilmaz O, Duester G, Morrison S. Aldehyde dehydrogenase 1a1 is dispensable for stem cell function in the mouse hematopoietic and nervous systems. Blood. 2009;113:1670-80 pubmed publisher..Finally, Aldh1a1 deficiency did not affect the function of stem cells from the adult central or peripheral nervous systems. Aldh1a1 is not a critical regulator of adult stem cell function or Aldefluor staining in mice. ..
- Chen Y, Gao X, Timar J, Tang D, Grossi I, Chelladurai M, et al. Identification of the alpha IIb beta 3 integrin in murine tumor cells. J Biol Chem. 1992;267:17314-20 pubmed..These experiments indicate that the alpha IIb beta 3-like protein in B16a cells is the authentic alpha IIb beta 3 and demonstrate, for the first time, that integrin alpha IIb beta 3 is not confined to megakaryocyte lineage cells.
- YougbarÃ© I, Lang S, Yang H, Chen P, Zhao X, Tai W, et al. Maternal anti-platelet Î²3 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. ..
- Echtler K, Konrad I, Lorenz M, Schneider S, Hofmaier S, Plenagl F, et al. Platelet GPIIb supports initial pulmonary retention but inhibits subsequent proliferation of melanoma cells during hematogenic metastasis. PLoS ONE. 2017;12:e0172788 pubmed publisher..Highly metastatic B16-D5 melanoma cells were injected intravenously into GPIIb-deficient (GPIIb-/-) or wildtype (WT) mice...
- Basani R, Zhu H, Thornton M, Soto C, Degrado W, Kowalska M, et al. Species differences in small molecule binding to alpha IIb beta 3 are the result of sequence differences in 2 loops of the alpha IIb beta propeller. Blood. 2009;113:902-10 pubmed publisher..residues 157, 159, and 162 in the W3:4-1 loop and an Asp-His replacement at residue 232 in the W4:4-1 loop of the alphaIIb beta propeller...
- Niki M, Nayak M, Jin H, Bhasin N, Plow E, Pandolfi P, et al. Dok-1 negatively regulates platelet integrin Î±IIbÎ²3 outside-in signalling and inhibits thrombosis in mice. Thromb Haemost. 2016;115:969-78 pubmed publisher..05 vs WT mice). We conclude that Dok-1 modulates thrombosis and haemostasis by negatively regulating Î±IIbÎ²3 outside-in signalling. ..
- Mitsios J, Prevost N, Kasirer Friede A, Gutierrez E, Groisman A, Abrams C, et al. What is vinculin needed for in platelets?. J Thromb Haemost. 2010;8:2294-304 pubmed publisher..Despite promoting membrane cytoskeleton integrity when mechanical force is applied to ?(IIb) ?(3) , vinculin is not required for the traditional functions of ?(IIb) ?(3) or the platelet actin cytoskeleton. ..
- Echtler K, Stark K, Lorenz M, Kerstan S, Walch A, Jennen L, et al. Platelets contribute to postnatal occlusion of the ductus arteriosus. Nat Med. 2010;16:75-82 pubmed publisher..A retrospective clinical study revealed that thrombocytopenia is an independent predictor for failure of DA closure in preterm human newborns, indicating that platelets are likely to contribute to DA closure in humans. ..
- Shivdasani R, Rosenblatt M, Zucker Franklin D, Jackson C, Hunt P, Saris C, et al. Transcription factor NF-E2 is required for platelet formation independent of the actions of thrombopoietin/MGDF in megakaryocyte development. Cell. 1995;81:695-704 pubmed..These findings provide insight into the genetic analysis of megakaryocyte maturation and thrombopoiesis. ..