Genomes and Genes
Gene Symbol: Itgb3
Description: integrin beta 3
Alias: CD61, GP3A, INGRB3, integrin beta-3, GPIIIa, platelet gpIIIa, platelet membrane glycoprotein IIIa
- Taverna D, Moher H, Crowley D, Borsig L, Varki A, Hynes R. Increased primary tumor growth in mice null for beta3- or beta3/beta5-integrins or selectins. Proc Natl Acad Sci U S A. 2004;101:763-8 pubmed..These results implicate cells of the innate immune system, macrophages or perhaps natural killer cells, in each case dependent on integrins and selectins, in tumor suppression. ..
- Petrich B, Fogelstrand P, Partridge A, Yousefi N, Ablooglu A, Shattil S, et al. The antithrombotic potential of selective blockade of talin-dependent integrin alpha IIb beta 3 (platelet GPIIb-IIIa) activation. J Clin Invest. 2007;117:2250-9 pubmed..Furthermore, they suggest that modulation of beta(3) integrin-talin interactions may provide an attractive target for antithrombotics and result in a reduced risk of pathological bleeding. ..
- Sloan E, Pouliot N, Stanley K, Chia J, Moseley J, Hards D, et al. Tumor-specific expression of alphavbeta3 integrin promotes spontaneous metastasis of breast cancer to bone. Breast Cancer Res. 2006;8:R20 pubmed
- Reynolds A, Reynolds L, Nagel T, Lively J, Robinson S, Hicklin D, et al. Elevated Flk1 (vascular endothelial growth factor receptor 2) signaling mediates enhanced angiogenesis in beta3-integrin-deficient mice. Cancer Res. 2004;64:8643-50 pubmed..These data confirm that VEGF signaling via Flk1 is enhanced in beta(3)-integrin-deficient mice and suggests that this increase may mediate the enhanced angiogenesis and tumor growth observed in these mice in vivo. ..
- Bakewell S, Nestor P, Prasad S, Tomasson M, Dowland N, Mehrotra M, et al. Platelet and osteoclast beta3 integrins are critical for bone metastasis. Proc Natl Acad Sci U S A. 2003;100:14205-10 pubmed..These data demonstrate a critical role for platelet alphaIIbbeta3 in tumor entry into bone and suggest a mechanism by which antiplatelet therapy may be beneficial in preventing the metastasis of solid tumors. ..
- Umemoto T, Yamato M, Ishihara J, Shiratsuchi Y, Utsumi M, Morita Y, et al. Integrin-?v?3 regulates thrombopoietin-mediated maintenance of hematopoietic stem cells. Blood. 2012;119:83-94 pubmed publisher..Thus, our findings demonstrate a mechanistic link between ?3-integrin and TPO in HSCs, which may contribute to maintenance of LTR activity in vivo as well as during ex vivo culture. ..
- Nemeth J, Cher M, Zhou Z, Mullins C, Bhagat S, Trikha M. Inhibition of alpha(v)beta3 integrin reduces angiogenesis, bone turnover, and tumor cell proliferation in experimental prostate cancer bone metastases. Clin Exp Metastasis. 2003;20:413-20 pubmed..Together these observations confirm the importance of alpha(v)beta3 in bone metabolism and angiogenesis, and point to the role of these processes in controlling growth of metastatic prostate cancer cells in the bone. ..
- 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 conclude that integrins are noncanonical Galpha13-coupled receptors that provide a mechanism for dynamic regulation of RhoA. ..
- Hermosilla T, Munoz D, Herrera Molina R, Valdivia A, Muñoz N, Nham S, et al. Direct Thy-1/alphaVbeta3 integrin interaction mediates neuron to astrocyte communication. Biochim Biophys Acta. 2008;1783:1111-20 pubmed publisher..Together, these results demonstrate that the alphavbeta3 integrin heterodimer interacts directly with Thy-1 present on neuronal cells to stimulate astrocytes. ..
- Robinson S, Reynolds L, Kostourou V, Reynolds A, da Silva R, Tavora B, et al. Alphav beta3 integrin limits the contribution of neuropilin-1 to vascular endothelial growth factor-induced angiogenesis. J Biol Chem. 2009;284:33966-81 pubmed publisher..Our data suggest that beta3 integrin may, in part, negatively regulate VEGF signaling by sequestering NRP1 and preventing it from interacting with VEGFR2. ..
- Moser M, Nieswandt B, Ussar S, Pozgajova M, Fassler R. Kindlin-3 is essential for integrin activation and platelet aggregation. Nat Med. 2008;14:325-30 pubmed publisher..We have therefore identified Kindlin-3 as a novel and essential element for platelet integrin activation in hemostasis and thrombosis. ..
- Pietri T, Thiery J, Dufour S. Differential expression of beta3 integrin gene in chick and mouse cranial neural crest cells. Dev Dyn. 2003;227:309-13 pubmed..Therefore, the difference in the beta3 integrin expression suggests that mouse and chicken cranial neural crest cells may have distinct integrin requirements during their ontogenesis. ..
- Wei C, Möller C, Altintas M, Li J, Schwarz K, Zacchigna S, et al. Modification of kidney barrier function by the urokinase receptor. Nat Med. 2008;14:55-63 pubmed..Blockade of alphavbeta3 integrin reduces podocyte motility in vitro and lowers proteinuria in mice. Our findings show a physiological role for uPAR signaling in the regulation of kidney permeability. ..
- Cluzel C, Saltel F, Lussi J, Paulhe F, Imhof B, Wehrle Haller B. The mechanisms and dynamics of (alpha)v(beta)3 integrin clustering in living cells. J Cell Biol. 2005;171:383-92 pubmed..Thus, integrin clustering requires the formation of the ternary complex consisting of activated integrins, immobilized ligands, talin, and PI(4,5)P2. The dynamic remodeling of this ternary complex controls cell motility. ..
- Steri V, Ellison T, Gontarczyk A, Weilbaecher K, Schneider J, Edwards D, et al. Acute depletion of endothelial ?3-integrin transiently inhibits tumor growth and angiogenesis in mice. Circ Res. 2014;114:79-91 pubmed publisher..Our findings imply that timing and length of inhibition are critical factors that need to be considered when targeting the endothelial expression of ?3-integrin to inhibit tumor growth and angiogenesis. ..
- Hodivala Dilke K, McHugh K, Tsakiris D, Rayburn H, Crowley D, Ullman Cullere M, et al. Beta3-integrin-deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival. J Clin Invest. 1999;103:229-38 pubmed
- Rao H, Lu G, Kajiya H, Garcia Palacios V, Kurihara N, Anderson J, et al. Alpha9beta1: a novel osteoclast integrin that regulates osteoclast formation and function. J Bone Miner Res. 2006;21:1657-65 pubmed..These results support a previously unknown role for alpha(9)beta(1) integrin in OCL formation and function. ..
- Carter M, Shah C, Muller C, Crawley J, Carneiro A, Veenstra Vanderweele J. Absence of preference for social novelty and increased grooming in integrin ?3 knockout mice: initial studies and future directions. Autism Res. 2011;4:57-67 pubmed publisher..The integrin ?3 receptor subunit gene (ITGB3) is a quantitative trait locus for whole blood 5-HT levels...
- Li L, Welser J, Milner R. Absence of the alpha v beta 3 integrin dictates the time-course of angiogenesis in the hypoxic central nervous system: accelerated endothelial proliferation correlates with compensatory increases in alpha 5 beta 1 integrin expression. J Cereb Blood Flow Metab. 2010;30:1031-43 pubmed publisher
- Chabadel A, Bañón Rodríguez I, Cluet D, Rudkin B, Wehrle Haller B, Genot E, et al. CD44 and beta3 integrin organize two functionally distinct actin-based domains in osteoclasts. Mol Biol Cell. 2007;18:4899-910 pubmed..However, although CD44 signals are sufficient to form a SZ, the presence of WIP is indispensable for the formation of a fully functional SZ. ..
- Svendsen O, Lidén A, Nedrebø T, Rubin K, Reed R. Integrin alphavbeta3 acts downstream of insulin in normalization of interstitial fluid pressure in sepsis and in cell-mediated collagen gel contraction. Am J Physiol Heart Circ Physiol. 2008;295:H555-60 pubmed publisher..Our findings suggest a beneficiary effect of insulin for patients with sepsis with regard to the fluid balance, and this effect may in part be due to a normalization of P(IF) by a mechanism involving the integrin alpha(v)beta(3). ..
- Kanamori M, Kawaguchi T, Berger M, Pieper R. Intracranial microenvironment reveals independent opposing functions of host alphaVbeta3 expression on glioma growth and angiogenesis. J Biol Chem. 2006;281:37256-64 pubmed..Appropriate management of these functions could lead to enhanced efficacy of anti-integrin based therapies for glioma. ..
- Schmidt S, Nakchbandi I, Ruppert R, Kawelke N, Hess M, Pfaller K, et al. Kindlin-3-mediated signaling from multiple integrin classes is required for osteoclast-mediated bone resorption. J Cell Biol. 2011;192:883-97 pubmed publisher..These findings show that osteoclasts require their entire integrin repertoire to be regulated by kindlin-3 to orchestrate bone homeostasis. ..
- Hamano Y, Zeisberg M, Sugimoto H, Lively J, Maeshima Y, Yang C, et al. Physiological levels of tumstatin, a fragment of collagen IV alpha3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via alphaV beta3 integrin. Cancer Cell. 2003;3:589-601 pubmed..These results indicate that MMP-generated fragments of basement membrane collagen can have endogenous function as integrin-mediated suppressors of pathologic angiogenesis and tumor growth. ..
- Reynolds L, Wyder L, Lively J, Taverna D, Robinson S, Huang X, et al. Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins. Nat Med. 2002;8:27-34 pubmed
- Sutherland A, Calarco P, Damsky C. Developmental regulation of integrin expression at the time of implantation in the mouse embryo. Development. 1993;119:1175-86 pubmed..abstract truncated at 400 words) ..
- Wu P, Lee S, Chuang C, Mori S, Akakura N, Wu W, et al. Non-cytotoxic cobra cardiotoxin A5 binds to alpha(v)beta3 integrin and inhibits bone resorption. Identification of cardiotoxins as non-RGD integrin-binding proteins of the Ly-6 family. J Biol Chem. 2006;281:7937-45 pubmed..These results identify CTX A5 as a non-RGD integrin-binding protein with therapeutic potential as an integrin antagonist. ..
- Taverna D, Crowley D, Connolly M, Bronson R, Hynes R. A direct test of potential roles for beta3 and beta5 integrins in growth and metastasis of murine mammary carcinomas. Cancer Res. 2005;65:10324-9 pubmed..These data indicate that alphavbeta3 or alphavbeta5 integrins are not essential for tumor growth and progression, although they might play some role in mammary gland development. ..
- Kanasaki K, Kanda Y, Palmsten K, Tanjore H, Lee S, LeBleu V, et al. Integrin beta1-mediated matrix assembly and signaling are critical for the normal development and function of the kidney glomerulus. Dev Biol. 2008;313:584-93 pubmed..Collectively, our studies demonstrate that podocyte beta1 integrin and ILK signaling is critical for postnatal development and function of the glomerular filtration apparatus. ..
- Ferkowicz M, Starr M, Xie X, Li W, Johnson S, Shelley W, et al. CD41 expression defines the onset of primitive and definitive hematopoiesis in the murine embryo. Development. 2003;130:4393-403 pubmed..CD41(bright) yolk sac definitive progenitor cells co-express CD61 and bind fibrinogen, demonstrating receptor function...
- Izawa T, Zou W, Chappel J, Ashley J, Feng X, Teitelbaum S. c-Src links a RANK/?v?3 integrin complex to the osteoclast cytoskeleton. Mol Cell Biol. 2012;32:2943-53 pubmed publisher..Thus, activated RANK prompts two distinct signaling pathways; one promotes osteoclast formation, and the other, in collaboration with c-Src-mediated linkage to ?v?3, organizes the cell's cytoskeleton. ..
- Weber G, Zawaideh S, Hikita S, Kumar V, Cantor H, Ashkar S. Phosphorylation-dependent interaction of osteopontin with its receptors regulates macrophage migration and activation. J Leukoc Biol. 2002;72:752-61 pubmed
- Milner R. Microglial expression of alphavbeta3 and alphavbeta5 integrins is regulated by cytokines and the extracellular matrix: beta5 integrin null microglia show no defects in adhesion or MMP-9 expression on vitronectin. Glia. 2009;57:714-23 pubmed publisher..Furthermore, it reveals that the alphavbeta5 integrin is not essential for mediating microglial adhesion and MMP-9 expression in response to vitronectin. ..
- Cho J, Kennedy D, Lin L, Huang M, Merrill Skoloff G, Furie B, et al. Protein disulfide isomerase capture during thrombus formation in vivo depends on the presence of ?3 integrins. Blood. 2012;120:647-55 pubmed publisher..These results indicate that both endothelial and platelet ?3 integrins contribute to extracellular PDI binding at the vascular injury site. ..
- Ren J, Avery J, Zhao H, Schneider J, Ross F, Muslin A. Beta3 integrin deficiency promotes cardiac hypertrophy and inflammation. J Mol Cell Cardiol. 2007;42:367-77 pubmed..These results suggest that alpha(v)beta(3) expression in bone marrow has a generalized suppressive effect on cardiac inflammation. ..
- Vaillant F, Asselin Labat M, Shackleton M, Forrest N, Lindeman G, Visvader J. The mammary progenitor marker CD61/beta3 integrin identifies cancer stem cells in mouse models of mammary tumorigenesis. Cancer Res. 2008;68:7711-7 pubmed publisher..In tumors arising in MMTV-wnt-1 tumors, the luminal epithelial progenitor marker CD61/beta3 integrin identified a cancer stem cell (CSC) population that was highly enriched for tumorigenic capability ..
- 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. ..
- Weis S, Lindquist J, Barnes L, Lutu Fuga K, Cui J, Wood M, et al. Cooperation between VEGF and beta3 integrin during cardiac vascular development. Blood. 2007;109:1962-70 pubmed..These findings show a clear vascular phenotype in the hearts of mice lacking beta3 and suggest this integrin plays a critical role in coronary vascular development and the vascular response to VEGF. ..
- Reynolds L, Conti F, Lucas M, Grose R, Robinson S, Stone M, et al. Accelerated re-epithelialization in beta3-integrin-deficient- mice is associated with enhanced TGF-beta1 signaling. Nat Med. 2005;11:167-74 pubmed..These data indicate that alpha(v)beta(3)-integrin can suppress TGF-beta1-mediated signaling, thereby controlling the rate of wound healing, and highlight a new mechanism for TGF-beta1 regulation by beta(3)-integrins. ..
- Arias Salgado E, Lizano S, Sarkar S, Brugge J, Ginsberg M, Shattil S. Src kinase activation by direct interaction with the integrin beta cytoplasmic domain. Proc Natl Acad Sci U S A. 2003;100:13298-302 pubmed..The data provide a paradigm for integrin regulation of Src and a molecular basis for the similar functional defects of osteoclasts or platelets from mice lacking beta3 integrins or c-Src. ..
- Faccio R, Takeshita S, Zallone A, Ross F, Teitelbaum S. c-Fms and the alphavbeta3 integrin collaborate during osteoclast differentiation. J Clin Invest. 2003;111:749-58 pubmed..Thus, while c-Fms and alpha(v)beta(3) collaborate in the osteoclastogenic process via shared activation of the ERK/c-Fos signaling pathway, the integrin is essential for matrix degradation. ..
- Danen E, Sonneveld P, Brakebusch C, Fassler R, Sonnenberg A. The fibronectin-binding integrins alpha5beta1 and alphavbeta3 differentially modulate RhoA-GTP loading, organization of cell matrix adhesions, and fibronectin fibrillogenesis. J Cell Biol. 2002;159:1071-86 pubmed..Our findings demonstrate that the pattern of fibronectin receptors expressed on a cell dictates the ability of fibronectin to stimulate RhoA-mediated organization of cell matrix adhesions. ..
- 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..It is proposed that this process may rapidly recruit platelets to sites of injury or inflammation in veins. ..
- Yang H, Reheman A, Chen P, Zhu G, Hynes R, Freedman J, et al. Fibrinogen and von Willebrand factor-independent platelet aggregation in vitro and in vivo. J Thromb Haemost. 2006;4:2230-7 pubmed..beta(3) integrin, thrombin, and Ca(2+) play critical roles in this Fg/VWF-independent aggregation, and both plasma and platelet granule proteins contribute to this process. ..
- Zhang Y, Chen Y, Krummel M, Rosen S. Autotaxin through lysophosphatidic acid stimulates polarization, motility, and transendothelial migration of naive T cells. J Immunol. 2012;189:3914-24 pubmed publisher..This entry role for LPA complements the efflux function of sphingosine 1-phosphate. ..
- Kim K, Hahm E, Li J, Holbrook L, Sasikumar P, Stanley R, et al. Platelet protein disulfide isomerase is required for thrombus formation but not for hemostasis in mice. Blood. 2013;122:1052-61 pubmed publisher..Tail bleeding time in platelet-specific PDI-deficient mice were not significantly increased. Our results provide important evidence that platelet PDI is essential for thrombus formation but not for hemostasis in mice. ..
- Andre P, Prasad K, Denis C, He M, Papalia J, Hynes R, et al. CD40L stabilizes arterial thrombi by a beta3 integrin--dependent mechanism. Nat Med. 2002;8:247-52 pubmed..In addition, rsCD40L promoted the aggregation of either human or mouse platelets under high shear rates. Thus, CD40L appears to be an alphaIIbbeta3 ligand, a platelet agonist, and necessary for stability of arterial thrombi. ..
- Smyth S, Reis E, Vaananen H, Zhang W, Coller B. Variable protection of beta 3-integrin--deficient mice from thrombosis initiated by different mechanisms. Blood. 2001;98:1055-62 pubmed..These results suggest that though alpha IIb beta 3 plays a dominant role in large-vessel thrombosis, it plays a variable role in systemic intravascular thrombosis. (Blood. 2001;98:1055-1062) ..
- Yang J, Zhu L, Zhang H, HIRBAWI J, Fukuda K, Dwivedi P, et al. Conformational activation of talin by RIAM triggers integrin-mediated cell adhesion. Nat Commun. 2014;5:5880 pubmed publisher..Our findings thus uncover a novel role for RIAM in conformational regulation of talin during integrin activation and cell adhesion. ..
- Tanaka S, Maekawa A, Matsubara L, Imanishi A, Yano M, Roeder R, et al. Periostin supports hematopoietic progenitor cells and niche-dependent myeloblastoma cells inÂ vitro. Biochem Biophys Res Commun. 2016;478:1706-12 pubmed publisher..These results suggest that stromal cell POSTN supports both normal HPCs and leukemia-initiating cells inÂ vitro, at least in part, indirectly by acting on stromal cells in an autocrine or paracrine manner. ..