integrin alpha2beta1

Summary

Summary: An integrin found on fibroblasts, platelets, endothelial and epithelial cells, and lymphocytes where it functions as a receptor for COLLAGEN and LAMININ. Although originally referred to as the collagen receptor, it is one of several receptors for collagen. Ligand binding to integrin alpha2beta1 triggers a cascade of intracellular signaling, including activation of p38 MAP kinase.

Top Publications

  1. Elton C, Smethurst P, Eggleton P, Farndale R. Physical and functional interaction between cell-surface calreticulin and the collagen receptors integrin alpha2beta1 and glycoprotein VI in human platelets. Thromb Haemost. 2002;88:648-54 pubmed
    ..In addition, these antibodies inhibited platelet adhesion to the integrin alpha2beta1-specific ligands, GFOGER-GPP and monomeric collagen I, and to the glycoprotein VI-specific ligand, CRP...
  2. Cheli Y, Kunicki T. hnRNP L regulates differences in expression of mouse integrin alpha2beta1. Blood. 2006;107:4391-8 pubmed
    There is a 2-fold variation in platelet integrin alpha2beta1 levels among inbred mouse strains...
  3. Kirkland S, Ying H. Alpha2beta1 integrin regulates lineage commitment in multipotent human colorectal cancer cells. J Biol Chem. 2008;283:27612-9 pubmed publisher
    ..This study indicates that the collagen receptor alpha2beta1 integrin is a regulator of cell fate in human multipotent colorectal cancer cells. ..
  4. Guidetti G, Greco F, Bertoni A, Giudici C, Viola M, Tenni R, et al. Platelet interaction with CNBr peptides from type II collagen via integrin alpha2beta1. Biochim Biophys Acta. 2003;1640:43-51 pubmed
    ..These results identify the CNBr peptides from collagen type II CB8 and CB11 as ligands for platelet integrin alpha(2)beta(1), and recognise their ability to support platelet adhesion and activation. ..
  5. Sasaki K, Tsuji T, Jinushi T, Matsuzaki J, Sato T, Chamoto K, et al. Differential regulation of VLA-2 expression on Th1 and Th2 cells: a novel marker for the classification of Th subsets. Int Immunol. 2003;15:701-10 pubmed
  6. Reyes C, Garcia A. Engineering integrin-specific surfaces with a triple-helical collagen-mimetic peptide. J Biomed Mater Res A. 2003;65:511-23 pubmed
    ..Engineering surfaces that specifically target certain integrin-ligand interactions and signaling cascades provides a biomolecular strategy for optimizing cellular responses in biomaterials and tissue engineering applications. ..
  7. Sabri S, Foudi A, Boukour S, Franc B, Charrier S, Jandrot Perrus M, et al. Deficiency in the Wiskott-Aldrich protein induces premature proplatelet formation and platelet production in the bone marrow compartment. Blood. 2006;108:134-40 pubmed
    ..In addition, they suggest a novel explanation for some of the platelet abnormalities characteristic of patients with WAS. ..
  8. Chung C, Wu W, Huang T. Aggretin, a snake venom-derived endothelial integrin alpha 2 beta 1 agonist, induces angiogenesis via expression of vascular endothelial growth factor. Blood. 2004;103:2105-13 pubmed
  9. Grzesiak J, Bouvet M. The alpha2beta1 integrin mediates the malignant phenotype on type I collagen in pancreatic cancer cell lines. Br J Cancer. 2006;94:1311-9 pubmed
    ..These results identify alpha2beta1 integrin-mediated adhesion to type I collagen as a potential therapeutic target in the treatment of pancreatic cancer. ..

More Information

Publications62

  1. Veit G, Zwolanek D, Eckes B, Niland S, Kapyla J, Zweers M, et al. Collagen XXIII, novel ligand for integrin alpha2beta1 in the epidermis. J Biol Chem. 2011;286:27804-13 pubmed publisher
    ..Furthermore, collagen XXIII is sufficient to induce adhesion and spreading of keratinocytes, a process that is significantly reduced in the absence of functional integrin ?(2)?(1). ..
  2. Raynal N, Hamaia S, Siljander P, Maddox B, Peachey A, Fernandez R, et al. Use of synthetic peptides to locate novel integrin alpha2beta1-binding motifs in human collagen III. J Biol Chem. 2006;281:3821-31 pubmed
    ..We describe two novel high affinity integrin-binding motifs in human collagen III (GROGER and GLOGEN) and a third motif (GLKGEN) that displays intermediate activity. Each motif was verified using shorter synthetic peptides. ..
  3. Wu Y, Zhao X, Pan S, Guo D, Wei R, Han J, et al. Salvianolic acid B inhibits platelet adhesion under conditions of flow by a mechanism involving the collagen receptor alpha2beta1. Thromb Res. 2008;123:298-305 pubmed publisher
    ..These combined results indicate that SAB inhibits platelet adhesion to immobilized collagen by interfering with the collagen receptor alpha2beta1. ..
  4. Yin H, Gerlach L, Miller M, Moore D, Liu D, Vilaire G, et al. Arylamide derivatives as allosteric inhibitors of the integrin alpha2beta1/type I collagen interaction. Bioorg Med Chem Lett. 2006;16:3380-2 pubmed
    ..Further we find that compound 4 recognizes a hydrophobic cleft on the side of the alpha(2) I-domain, suggesting an alternative targeting site for drug development. ..
  5. Lu Z, Zreiqat H. Beta-tricalcium phosphate exerts osteoconductivity through alpha2beta1 integrin and down-stream MAPK/ERK signaling pathway. Biochem Biophys Res Commun. 2010;394:323-9 pubmed publisher
  6. Kim H, Oh D, Lee S, Ha J, Joe Y. Antimigratory effect of TK1-2 is mediated in part by interfering with integrin alpha2beta1. Mol Cancer Ther. 2008;7:2133-41 pubmed publisher
    ..Therefore, these results suggest that TK1-2 inhibits endothelial cell migration through inhibition of signaling and cytoskeleton rearrangement in part by interfering with integrin alpha(2)beta(1). ..
  7. Karjalainen M, Kakkonen E, Upla P, Paloranta H, Kankaanpää P, Liberali P, et al. A Raft-derived, Pak1-regulated entry participates in alpha2beta1 integrin-dependent sorting to caveosomes. Mol Biol Cell. 2008;19:2857-69 pubmed publisher
    ..Our results together suggest that alpha2beta1 integrin clustering defines its own entry pathway that is Pak1 dependent but clathrin and caveolin independent and that is able to sort cargo to caveosomes. ..
  8. Slatter D, Foley L, Peachey A, Nietlispach D, Farndale R. Rapid synthesis of a register-specific heterotrimeric type I collagen helix encompassing the integrin alpha2beta1 binding site. J Mol Biol. 2006;359:289-98 pubmed
    ..Less flexible spacers between the disulphide linkages and the helix will restrict each heterotrimer to one register only. ..
  9. Vuoriluoto K, Jokinen J, Kallio K, Salmivirta M, Heino J, Ivaska J. Syndecan-1 supports integrin alpha2beta1-mediated adhesion to collagen. Exp Cell Res. 2008;314:3369-81 pubmed publisher
    ..Here we show that cell-surface heparan sulphate proteoglycans (HSPGs) support integrin alpha2beta1-mediated adhesion to collagen...
  10. Miller M, Basra S, Kulp D, Billings P, Choi S, Beavers M, et al. Small-molecule inhibitors of integrin alpha2beta1 that prevent pathological thrombus formation via an allosteric mechanism. Proc Natl Acad Sci U S A. 2009;106:719-24 pubmed publisher
    ..These results suggest that targeting integrin alpha(2)beta(1) could be a potentially safe, effective approach to long-term therapy for cardiovascular disease. ..
  11. Staniszewska I, Walsh E, Rothman V, Gaathon A, Tuszynski G, Calvete J, et al. Effect of VP12 and viperistatin on inhibition of collagen-receptor-dependent melanoma metastasis. Cancer Biol Ther. 2009;8:1507-16 pubmed
    ..These data suggest that collagen receptors may be an interesting target for development of new anti-metastatic therapies...
  12. Valdramidou D, Humphries M, Mould A. Distinct roles of beta1 metal ion-dependent adhesion site (MIDAS), adjacent to MIDAS (ADMIDAS), and ligand-associated metal-binding site (LIMBS) cation-binding sites in ligand recognition by integrin alpha2beta1. J Biol Chem. 2008;283:32704-14 pubmed publisher
  13. Arlinghaus F, Eble J. C-type lectin-like proteins from snake venoms. Toxicon. 2012;60:512-9 pubmed publisher
    ..Along with EMS16 and VP12, rhodocetin inhibits collagen-binding to the ?2A-domain. These integrin-specific antagonists are lead structures for the development of antimetastatic and antiangiogenic drugs...
  14. Grundström G, Mosher D, Sakai T, Rubin K. Integrin alphavbeta3 mediates platelet-derived growth factor-BB-stimulated collagen gel contraction in cells expressing signaling deficient integrin alpha2beta1. Exp Cell Res. 2003;291:463-73 pubmed
    ..Our results show that PDGF-BB stimulation of fibroblast-collagen interactions is mediated by the alphavbeta3 integrin when beta1 integrin function is impaired. ..
  15. Ramirez N, Zhang Z, Madamanchi A, Boyd K, O Rear L, Nashabi A, et al. The ???? integrin is a metastasis suppressor in mouse models and human cancer. J Clin Invest. 2011;121:226-37 pubmed publisher
    ..Thus, the ?2?1 integrin functionally inhibits breast tumor metastasis, and ?2 expression may serve as an important biomarker of metastatic potential and patient survival. ..
  16. Abair T, Sundaramoorthy M, Chen D, Heino J, Ivaska J, Hudson B, et al. Cross-talk between integrins alpha1beta1 and alpha2beta1 in renal epithelial cells. Exp Cell Res. 2008;314:3593-604 pubmed publisher
    ..both integrins are expressed in the same cell, it has been suggested that alpha1beta1 negatively regulates integrin alpha2beta1-dependent functions...
  17. Lin M, Chang C, Lin B, Yang H, Chu C, Wu M, et al. Elevated expression of Cyr61 enhances peritoneal dissemination of gastric cancer cells through integrin alpha2beta1. J Biol Chem. 2007;282:34594-604 pubmed
    ..The data suggest that Cyr61 may contribute to the peritoneal dissemination of gastric cancer by promoting tumor-cell adhesion ability through the up-regulation of the functional integrin alpha(2)beta(1) via an AP-1-dependent pathway. ..
  18. Calvo E, Tokumasu F, Marinotti O, Villeval J, Ribeiro J, Francischetti I. Aegyptin, a novel mosquito salivary gland protein, specifically binds to collagen and prevents its interaction with platelet glycoprotein VI, integrin alpha2beta1, and von Willebrand factor. J Biol Chem. 2007;282:26928-38 pubmed
    ..These findings suggest that aegyptin recognizes specific binding sites for glycoprotein VI, integrin alpha2beta1, and vWf, thereby preventing collagen interaction with its three major ligands...
  19. Horii K, Okuda D, Morita T, Mizuno H. Crystal structure of EMS16 in complex with the integrin alpha2-I domain. J Mol Biol. 2004;341:519-27 pubmed
    ..EMS16 from the venom of Echis multisquamatus binds to the collagen receptor, integrin alpha2beta1, also known as glycoprotein (GP) Ia/IIa, and specifically inhibits collagen binding...
  20. San Antonio J, Zoeller J, Habursky K, Turner K, Pimtong W, Burrows M, et al. A key role for the integrin alpha2beta1 in experimental and developmental angiogenesis. Am J Pathol. 2009;175:1338-47 pubmed publisher
    ..Collectively, our results provide strong biochemical and genetic evidence of a central role for alpha2beta1 integrin in experimental and developmental angiogenesis. ..
  21. Khalsa P, Ge W, Uddin M, Hadjiargyrou M. Integrin alpha2beta1 affects mechano-transduction in slowly and rapidly adapting cutaneous mechanoreceptors in rat hairy skin. Neuroscience. 2004;129:447-59 pubmed
    The role of a transmembrane protein, integrin alpha2beta1, to modulate the neural responses of cutaneous mechanoreceptors to mechanical indentation was examined using an isolated skin-nerve preparation in a rat model...
  22. Eble J, Niland S, Bracht T, Mormann M, Peter Katalinic J, Pohlentz G, et al. The alpha2beta1 integrin-specific antagonist rhodocetin is a cruciform, heterotetrameric molecule. FASEB J. 2009;23:2917-27 pubmed publisher
    The integrin alpha2beta1 plays an important role in various pathophysiological processes, such as thrombosis, wound healing, inflammation, and metastasis...
  23. 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. ..
  24. Sabri S, Jandrot Perrus M, Bertoglio J, Farndale R, Mas V, Debili N, et al. Differential regulation of actin stress fiber assembly and proplatelet formation by alpha2beta1 integrin and GPVI in human megakaryocytes. Blood. 2004;104:3117-25 pubmed
    ..Thus, proplatelet formation in human MKs could be tightly regulated by differential interactions with their collagen receptors. We propose that this interaction with collagen prevents proplatelet formation within the marrow. ..
  25. Whelan M, Senger D. Collagen I initiates endothelial cell morphogenesis by inducing actin polymerization through suppression of cyclic AMP and protein kinase A. J Biol Chem. 2003;278:327-34 pubmed
  26. Chung C, Lin K, Chang C, Peng H, Huang T. The integrin alpha2beta1 agonist, aggretin, promotes proliferation and migration of VSMC through NF-kB translocation and PDGF production. Br J Pharmacol. 2009;156:846-56 pubmed publisher
    ..Here, we investigate the mechanism of VSMC migration and proliferation caused by aggretin, a snake venom integrin alpha2beta1 agonist...
  27. Friedrichs J, Manninen A, Muller D, Helenius J. Galectin-3 regulates integrin alpha2beta1-mediated adhesion to collagen-I and -IV. J Biol Chem. 2008;283:32264-72 pubmed publisher
    ..We propose that galectin-3 influences integrin alpha(2)beta(1)-mediated adhesion complex formation by altering receptor clustering. ..
  28. Eble J, Niland S, Dennes A, Schmidt Hederich A, Bruckner P, Brunner G. Rhodocetin antagonizes stromal tumor invasion in vitro and other alpha2beta1 integrin-mediated cell functions. Matrix Biol. 2002;21:547-58 pubmed
    ..Rhodocetin might be therapeutically useful because of its lack of interference with RGD-dependent integrins, low molecular mass, high solubility, and biochemical stability. ..
  29. Cole V, Staton J, Eikelboom J, Hankey G, Yi Q, Shen Y, et al. Collagen platelet receptor polymorphisms integrin alpha2beta1 C807T and GPVI Q317L and risk of ischemic stroke. J Thromb Haemost. 2003;1:963-70 pubmed
    Several polymorphisms of integrin alpha2beta1 and glycoprotein (GP) VI that may modify platelet-collagen interactions or subsequent signaling have been described...
  30. Rintanen N, Karjalainen M, Alanko J, Paavolainen L, Mäki A, Nissinen L, et al. Calpains promote ?2?1 integrin turnover in nonrecycling integrin pathway. Mol Biol Cell. 2012;23:448-63 pubmed publisher
    ..In conclusion, we identified a novel virus- and clustering-specific pathway that diverts ?2?1 integrin from its normal endo/exocytic traffic to a nonrecycling, calpain-dependent degradative endosomal route. ..
  31. Pula G, Poole A. Critical roles for the actin cytoskeleton and cdc42 in regulating platelet integrin alpha2beta1. Platelets. 2008;19:199-210 pubmed publisher
    ..two-site model for platelet activation by collagen requires tight binding of platelets to collagen through integrin alpha2beta1, after its prior activation by inside-out signals initiated by GP VI...
  32. Bernardi B, Guidetti G, Campus F, Crittenden J, Graybiel A, Balduini C, et al. The small GTPase Rap1b regulates the cross talk between platelet integrin alpha2beta1 and integrin alphaIIbbeta3. Blood. 2006;107:2728-35 pubmed
    The involvement of the small GTPase Rap1b in platelet integrin alpha2beta1-dependent outside-in signaling was investigated...
  33. Liberali P, Kakkonen E, Turacchio G, Valente C, Spaar A, Perinetti G, et al. The closure of Pak1-dependent macropinosomes requires the phosphorylation of CtBP1/BARS. EMBO J. 2008;27:970-81 pubmed publisher
    ..These results provide an insight into the molecular mechanisms of CtBP1/BARS activation in membrane fissioning, and extend the relevance of CtBP1/BARS-induced fission to human viral infection. ..
  34. Choi S, Vilaire G, Marcinkiewicz C, Winkler J, Bennett J, Degrado W. Small molecule inhibitors of integrin alpha2beta1. J Med Chem. 2007;50:5457-62 pubmed
  35. Grzesiak J, Smith K, Burton D, Deftos L, Bouvet M. GSK3 and PKB/Akt are associated with integrin-mediated regulation of PTHrP, IL-6 and IL-8 expression in FG pancreatic cancer cells. Int J Cancer. 2005;114:522-30 pubmed
    ..These results implicate GSK3 and PKB/Akt in the integrin-mediated regulation of PTHrP, IL-6 and IL-8 in pancreatic cancer. ..
  36. Wang C, Su H, Hsu Y, Shen M, Tang M. A discoidin domain receptor 1/SHP-2 signaling complex inhibits alpha2beta1-integrin-mediated signal transducers and activators of transcription 1/3 activation and cell migration. Mol Biol Cell. 2006;17:2839-52 pubmed
    ..Together, these results demonstrate that SHP-2 is required for the DDR1-induced suppression of Stat1 and Stat3 tyrosine phosphorylation, cell migration, and branching tubulogenesis. ..
  37. Karjalainen M, Rintanen N, Lehkonen M, Kallio K, Mäki A, Hellström K, et al. Echovirus 1 infection depends on biogenesis of novel multivesicular bodies. Cell Microbiol. 2011;13:1975-95 pubmed publisher
    ..Our results show that the non-enveloped EV1 depends on biogenesis of novel multivesicular structures for successful infection...
  38. Suh H, Han H. Collagen I regulates the self-renewal of mouse embryonic stem cells through ?2?1 integrin- and DDR1-dependent Bmi-1. J Cell Physiol. 2011;226:3422-32 pubmed publisher
    ..These results indicate that collagen I stimulates the self-renewal of mESCs mediated by Bmi-1 through ?2?1 integrin-dependent ILK, Notch, Gli-1, and DDR1-dependent Ras, PI3K/Akt, and ERK. ..
  39. Malara A, Gruppi C, Pallotta I, Spedden E, Tenni R, Raspanti M, et al. Extracellular matrix structure and nano-mechanics determine megakaryocyte function. Blood. 2011;118:4449-53 pubmed publisher
    ..On the contrary, a decrease in mechanical tension caused by N-acetylation of lysine side chains in type I collagen completely reverted these processes by preventing fibrillogenesis...
  40. Xu H, Bihan D, Chang F, Huang P, Farndale R, Leitinger B. Discoidin domain receptors promote α1β1- and α2β1-integrin mediated cell adhesion to collagen by enhancing integrin activation. PLoS ONE. 2012;7:e52209 pubmed publisher
    ..Our data thus demonstrate an adhesion-promoting role of the DDRs, whereby overexpression and/or activation of the DDRs leads to enhanced integrin-mediated cell adhesion as a result of higher integrin activation state. ..
  41. Olivares Navarrete R, Raz P, Zhao G, Chen J, Wieland M, Cochran D, et al. Integrin alpha2beta1 plays a critical role in osteoblast response to micron-scale surface structure and surface energy of titanium substrates. Proc Natl Acad Sci U S A. 2008;105:15767-72 pubmed publisher
  42. Fiedler L, Schonherr E, Waddington R, Niland S, Seidler D, Aeschlimann D, et al. Decorin regulates endothelial cell motility on collagen I through activation of insulin-like growth factor I receptor and modulation of alpha2beta1 integrin activity. J Biol Chem. 2008;283:17406-15 pubmed publisher
  43. Shintani Y, Fukumoto Y, Chaika N, Svoboda R, Wheelock M, Johnson K. Collagen I-mediated up-regulation of N-cadherin requires cooperative signals from integrins and discoidin domain receptor 1. J Cell Biol. 2008;180:1277-89 pubmed publisher
    ..Both receptor complexes rely on the p130 Crk-associated substrate scaffold. Interestingly, Rap1, but not Rho family guanosine triphosphatases, is required for the response to collagen I. ..
  44. Grenache D, Zhang Z, Wells L, Santoro S, Davidson J, Zutter M. Wound healing in the alpha2beta1 integrin-deficient mouse: altered keratinocyte biology and dysregulated matrix metalloproteinase expression. J Invest Dermatol. 2007;127:455-66 pubmed
  45. McBrien N, Metlapally R, Jobling A, Gentle A. Expression of collagen-binding integrin receptors in the mammalian sclera and their regulation during the development of myopia. Invest Ophthalmol Vis Sci. 2006;47:4674-82 pubmed
    ..This study identified the major collagen-binding integrin receptors in the mammalian sclera and investigated their mRNA expression during the development of and recovery from experimental myopia...
  46. Znoyko I, Trojanowska M, Reuben A. Collagen binding alpha2beta1 and alpha1beta1 integrins play contrasting roles in regulation of Ets-1 expression in human liver myofibroblasts. Mol Cell Biochem. 2006;282:89-99 pubmed
  47. Sarratt K, Chen H, Zutter M, Santoro S, Hammer D, Kahn M. GPVI and alpha2beta1 play independent critical roles during platelet adhesion and aggregate formation to collagen under flow. Blood. 2005;106:1268-77 pubmed
    The roles of the 2 major platelet-collagen receptors, glycoprotein VI (GPVI) and integrin alpha2beta1, have been intensely investigated using a variety of methods over the past decade...
  48. Jokinen J, Dadu E, Nykvist P, Kapyla J, White D, Ivaska J, et al. Integrin-mediated cell adhesion to type I collagen fibrils. J Biol Chem. 2004;279:31956-63 pubmed
  49. Whittard J, Craig S, Mould A, Koch A, Pertz O, Engel J, et al. E-cadherin is a ligand for integrin alpha2beta1. Matrix Biol. 2002;21:525-32 pubmed
    ..These findings demonstrate that E-cadherin can interact with alpha2beta1 and suggest that heterotypic interactions between E-cadherin and integrins may be more common than originally thought. ..
  50. Chiu Y, Shieh D, Tong K, Chen C, Huang K, Chen P, et al. Involvement of AdipoR receptor in adiponectin-induced motility and alpha2beta1 integrin upregulation in human chondrosarcoma cells. Carcinogenesis. 2009;30:1651-9 pubmed publisher
    ..One mechanism underlying adiponectin-directed migration was transcriptional upregulation of alpha2beta1 integrin and activation of AdipoR receptor, AMPK, p38 and NF-kappaB pathways. ..
  51. Pallotta I, Lovett M, Rice W, Kaplan D, Balduini A. Bone marrow osteoblastic niche: a new model to study physiological regulation of megakaryopoiesis. PLoS ONE. 2009;4:e8359 pubmed publisher
    ..These findings serve as an important step in developing suitable in vitro systems to use for the study and manipulation of Mk differentiation and maturation in both normal and diseased states. ..
  52. White T, Berny M, Robinson D, Yin H, Degrado W, Hanson S, et al. The leech product saratin is a potent inhibitor of platelet integrin alpha2beta1 and von Willebrand factor binding to collagen. FEBS J. 2007;274:1481-91 pubmed
    ..These results demonstrate that saratin interferes with integrin alpha2beta1 binding to collagen in addition to inhibiting von Willebrand factor-collagen binding, presumably by binding ..
  53. Emsley J, Knight C, Farndale R, Barnes M. Structure of the integrin alpha2beta1-binding collagen peptide. J Mol Biol. 2004;335:1019-28 pubmed
    ..This flexibility could be important to the integrin-collagen interaction and provides a possible explanation for the unique orientation of the three GFOGER strands observed in the integrin-IBP(c) complex crystal structure. ..