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Chemical Compound Review

Integrin     5,6-dimethoxy-2-methyl-3-[2- (4...

Synonyms: Opertil, Oxipertina, Oxipertine, oxypertine, Equipertine, ...
 
 
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Disease relevance of Integrin

  • These results indicate that beta 4 integrin promotes tumor progression by amplifying ErbB2 signaling and identify beta 4 as a potential target for molecular therapy of breast cancer [1].
  • These data indicate that adenovirus attachment and uptake into cells are separate but cooperative events that result from the interaction of distinct viral coat proteins with a receptor for attachment and alpha v integrin receptors for internalization [2].
  • Our AAV/phage (AAVP) prototype targets an integrin [3].
  • To address the role of integrin alpha7 in human muscle disease, we determined alpha7 protein expression in muscle biopsies from 117 patients with unclassified congenital myopathy and congenital muscular dystrophy by immunocytochemistry [4].
  • Suprabasal integrin expression in the epidermis of transgenic mice results in developmental defects and a phenotype resembling psoriasis [5].
  • Taken together, our findings suggest that Src TKs play a critical role in LPS-induced activations of NF-kappaB and integrin (alpha(v)beta(3)) signaling during acute lung injury [6].
  • Our results underscore the importance of a proper balance in the adhesion and de-adhesion of the alpha4beta7 integrin, both for lymphocyte trafficking to the gut and for colitis progression [7].
  • Binding of Pur alpha to the HIF-1-independent beta(2) integrin promoters is induced by hypoxia and mutagenesis of these Pur alpha-binding sites almost completely abolishes the ability of the promoters to respond to hypoxic conditions [8].
  • As a result, prostate cancer cells expressing fully functional but not dis-regulated alphavbeta3 integrin are able to control their own adherence and migration to bone matrix, functions that facilitate tumor growth and control bone lesion development [9].
  • Reconstitution of integrin beta(3) in HCC may be a potential therapeutic approach to inhibit aggressive growth of liver cancer [10].
  • These findings indicate that integrin β1 has a major impact on HNSCC prognosis through its regulation of metastasis [11].
 

Psychiatry related information on Integrin

 

High impact information on Integrin

 

Chemical compound and disease context of Integrin

 

Biological context of Integrin

  • In this review, we discuss the role of integrins in T cell-mediated immunity, with a focus on how these receptors participate in lymphocyte recirculation and T cell activation, how antigen stimulation regulates integrin activity, and how integrins define functionally unique subsets of T cells and APCs [18].
  • We show here that multiple members of the integrin superfamily of cell adhesion receptors bind the Y. pseudotuberculosis invasin protein prior to bacterial penetration into mammalian cells [27].
  • This change promotes phosphorylation of p130Cas by Src family kinases and the transduction of integrin-mediated signaling [28].
  • After angiogenesis is initiated, antagonists of this integrin induce apoptosis of the proliferative angiogenic vascular cells, leaving preexisting quiescent blood vessels unaffected [29].
  • Thus, fibrillar collagen specifically regulates early integrin signaling that may lead to up-regulation of cdk2 inhibitors and inhibition of SMC proliferation [30].
 

Anatomical context of Integrin

  • Although multiple integrins on airway epithelial cells may support adhesion to the same ligands, the functional roles of each integrin that has been examined in detail are quite distinct [31].
  • We have located distinct integrin-directed endothelial cell and platelet attachment sites on immobilized fibrinogen using a combination of synthetic peptides, fibrinogen fragments, and specific anti-peptide monoclonal antibodies [32].
  • Further supporting the role of alpha 2 beta 1, cell lines expressing minimal levels of this integrin uniformly failed to contract collagen matrices [33].
  • Tenascin inhibits integrin-mediated chick fibroblast attachment to fibronectin, laminin, and the GRGDS peptide [34].
  • Integrin expression is normally confined to the basal layer of the epidermis, but when epidermal homeostasis is perturbed, the receptors are also expressed by suprabasal, differentiating keratinocytes [5].
 

Associations of Integrin with other chemical compounds

  • Integration of receptor tyrosine kinase, integrin, and cadherin activities is crucial for normal cell growth, motility, and adhesion [35].
  • Structure of integrin, a glycoprotein involved in the transmembrane linkage between fibronectin and actin [36].
  • We have used the involucrin promoter to express functional human integrin subunits alpha 2, alpha 5, and beta 1 in the suprabasal epidermal layers of transgenic mice [5].
  • FHA interacts with two classes of molecules on macrophages, galactose-containing glycoconjugates and the integrin CR3 (alpha M beta 2, CD11b/CD18) [37].
  • The activity-dependent reduction in Pr and a switch in the subunit composition of synaptic NMDA receptors was prevented by chronic blockade with peptides containing the integrin-binding site Arg-Gly-Asp (RGD), or by a functional antibody against the beta3 integrin subunit [38].
  • The information obtained here may guide the future development of RGD peptide-based imaging and internal radiotherapeutic agents targeting integrin alpha(v)beta(3) [39].
  • Taken together, these findings provide novel genetic evidence that a ROS-Fer signaling arm contributes to SFK-mediated Ctn tyrosine phosphorylation in integrin signaling [40].
  • These data demonstrate an important role of the Arg/Lys finger in formation of a stable integrin heterodimer, and suggest that subtle changes at this residue affect the activation state of the integrin [41].
  • We propose that the unbending of the integrin molecule after guanine nucleotide-binding protein-coupled receptor-induced signaling accounts for the enhanced rate of HUTS-21 binding [42].
  • Testosterone and 17beta-estradiol had no influence on integrin levels, but cortisol up-regulated expression of the alpha5 subunit in a time-dependent and dose-dependent manner [43].
  • We have engineered highly stable cystine knot peptides with potent and specific integrin α(v)β(6)-binding activities for cancer detection [44].
 

Gene context of Integrin

  • We describe here a protein, cytohesin-1, which specifically interacts with the intracellular portion of the integrin beta 2 chain (CD18) [45].
  • To study the potential involvement of alpha 7 integrin, during myogenesis and its role in muscle integrity and function, we generated a null allele of the alpha 7 gene (Itga7) in the germline of mice by homologous recombination in embryonic stem (ES) cells [46].
  • Previously, in different JEB phenotypes, mutations have been found in the three genes for the anchoring filament component laminin 5 (LAMA3, LAMB3, and LAMC2) and in the gene for the hemidesmosome-associated integrin beta 4 subunit [47].
  • These effects require alpha 3 beta 1 integrin-mediated binding of TIMP-2 to endothelial cells [48].
  • To determine if any of these three patients had mutations of the integrin alpha7 gene, ITGA7, we cloned and sequenced the full-length human ITGA7 cDNA, and screened the patients for mutations [4].
  • This novel interaction between integrin alpha(4)beta(1) in sickle red cells and endothelial Lu/BCAM proteins could participate in sickle cell adhesion to endothelium and potentially play a role in vaso-occlusive episodes [49].
  • Because Numb interacts with the aPKC binding partner PAR-3, we propose a model in which polarized Numb phosphorylation contributes to cell migration by directing integrin endocytosis to the leading edge [50].
  • Up-regulation of CD40L expression and T cell proliferation, induced by beta1 integrin stimulation, were completely inhibited by transfection of the dominant-negative truncations of FAK or WT PTEN [51].
  • Either HGF or Listeria InlB bound to c-met and either C1q or type I collagen bound to alpha2beta1 integrin stimulates PMC activation [52].
  • When taken together, our results describe a novel and unique mechanism of coordinated interactions of the integrin alpha9 cytoplasmic domain, Src tyrosine kinase and iNOS to transduce integrin-alpha9beta1-mediated cell migration [53].
  • Analysis of NPCs cultured ex vivo reveals that the growth and survival defects correlate, in part, with diminished integrin-mediated activation of latent transforming growth factor beta1 (TGFbeta1), which is an ECM protein ligand for alphavbeta8 integrin [54].
  • We demonstrate that alpha3beta1 integrin, a major laminin receptor involved in the development of the kidney, and c-Met, the receptor for hepatocyte growth factor, signal coordinately to regulate the expression of Wnt7b in the mouse [55].
 

Analytical, diagnostic and therapeutic context of Integrin

  • Mutagenesis and dominant-negative inhibition studies reveal that Shc is necessary and sufficient for activation of the MAP kinase pathway in response to integrin ligation [56].
  • This study supports the idea that alphaVbeta5 integrin serves as a co-receptor for AAV-2 virions, and should have a substantial effect on the use of AAV vectors in human gene therapy [24].
  • Strategies based on blocking beta1 integrin-mediated survival signals may represent a new therapeutic approach to improve the response to chemotherapy in SCLC [57].
  • Finally, polyclonal antibodies against the integrin beta 1 subunit of VLA-4 inhibit the formation of CFU-S12-derived spleen colonies and medullary haematopoiesis in vivo following intravenous infusion of antibody-treated bone marrow cells [58].
  • While there has been a rapid progress in the understanding of integrin structure, elucidation of signaling events to relay extracellular signaling to integrins in physiological contexts has recently emerged from studies using gene-targeting and gene-silencing technique [59].

References

  1. Beta 4 integrin amplifies ErbB2 signaling to promote mammary tumorigenesis. Guo, W., Pylayeva, Y., Pepe, A., Yoshioka, T., Muller, W.J., Inghirami, G., Giancotti, F.G. Cell (2006) [Pubmed]
  2. Integrins alpha v beta 3 and alpha v beta 5 promote adenovirus internalization but not virus attachment. Wickham, T.J., Mathias, P., Cheresh, D.A., Nemerow, G.R. Cell (1993) [Pubmed]
  3. A hybrid vector for ligand-directed tumor targeting and molecular imaging. Hajitou, A., Trepel, M., Lilley, C.E., Soghomonyan, S., Alauddin, M.M., Marini, F.C., Restel, B.H., Ozawa, M.G., Moya, C.A., Rangel, R., Sun, Y., Zaoui, K., Schmidt, M., von Kalle, C., Weitzman, M.D., Gelovani, J.G., Pasqualini, R., Arap, W. Cell (2006) [Pubmed]
  4. Mutations in the integrin alpha7 gene cause congenital myopathy. Hayashi, Y.K., Chou, F.L., Engvall, E., Ogawa, M., Matsuda, C., Hirabayashi, S., Yokochi, K., Ziober, B.L., Kramer, R.H., Kaufman, S.J., Ozawa, E., Goto, Y., Nonaka, I., Tsukahara, T., Wang, J.Z., Hoffman, E.P., Arahata, K. Nat. Genet. (1998) [Pubmed]
  5. Suprabasal integrin expression in the epidermis of transgenic mice results in developmental defects and a phenotype resembling psoriasis. Carroll, J.M., Romero, M.R., Watt, F.M. Cell (1995) [Pubmed]
  6. Src tyrosine kinases mediate activations of NF-kappaB and integrin signal during lipopolysaccharide-induced acute lung injury. Lee, H.S., Moon, C., Lee, H.W., Park, E.M., Cho, M.S., Kang, J.L. J. Immunol. (2007) [Pubmed]
  7. Aberrant activation of integrin alpha4beta7 suppresses lymphocyte migration to the gut. Park, E.J., Mora, J.R., Carman, C.V., Chen, J., Sasaki, Y., Cheng, G., von Andrian, U.H., Shimaoka, M. J. Clin. Invest. (2007) [Pubmed]
  8. Identification of Pur alpha as a new hypoxia response factor responsible for coordinated induction of the beta 2 integrin family. Kong, T., Scully, M., Shelley, C.S., Colgan, S.P. J. Immunol. (2007) [Pubmed]
  9. Prostate cancer specific integrin alphavbeta3 modulates bone metastatic growth and tissue remodeling. McCabe, N.P., De, S., Vasanji, A., Brainard, J., Byzova, T.V. Oncogene (2007) [Pubmed]
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  13. Extracellular K(+) and opening of voltage-gated potassium channels activate T cell integrin function: physical and functional association between Kv1.3 channels and beta1 integrins. Levite, M., Cahalon, L., Peretz, A., Hershkoviz, R., Sobko, A., Ariel, A., Desai, R., Attali, B., Lider, O. J. Exp. Med. (2000) [Pubmed]
  14. The alpha5beta1 integrin mediates elimination of amyloid-beta peptide and protects against apoptosis. Matter, M.L., Zhang, Z., Nordstedt, C., Ruoslahti, E. J. Cell Biol. (1998) [Pubmed]
  15. Interaction of West Nile virus with alpha v beta 3 integrin mediates virus entry into cells. Chu, J.J., Ng, M.L. J. Biol. Chem. (2004) [Pubmed]
  16. Constitutive and induced phosphorylation of the alpha- and beta-chains of the CD11/CD18 leukocyte integrin family. Relationship to adhesion-dependent functions. Buyon, J.P., Slade, S.G., Reibman, J., Abramson, S.B., Philips, M.R., Weissmann, G., Winchester, R. J. Immunol. (1990) [Pubmed]
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  18. Integrins and T cell-mediated immunity. Pribila, J.T., Quale, A.C., Mueller, K.L., Shimizu, Y. Annu. Rev. Immunol. (2004) [Pubmed]
  19. CD45: a critical regulator of signaling thresholds in immune cells. Hermiston, M.L., Xu, Z., Weiss, A. Annu. Rev. Immunol. (2003) [Pubmed]
  20. VLA proteins in the integrin family: structures, functions, and their role on leukocytes. Hemler, M.E. Annu. Rev. Immunol. (1990) [Pubmed]
  21. Paxillin: adapting to change. Brown, M.C., Turner, C.E. Physiol. Rev. (2004) [Pubmed]
  22. A discrete sequence in a platelet integrin is involved in ligand recognition. D'Souza, S.E., Ginsberg, M.H., Matsueda, G.R., Plow, E.F. Nature (1991) [Pubmed]
  23. Structure of a major immunogenic site on foot-and-mouth disease virus. Logan, D., Abu-Ghazaleh, R., Blakemore, W., Curry, S., Jackson, T., King, A., Lea, S., Lewis, R., Newman, J., Parry, N. Nature (1993) [Pubmed]
  24. AlphaVbeta5 integrin: a co-receptor for adeno-associated virus type 2 infection. Summerford, C., Bartlett, J.S., Samulski, R.J. Nat. Med. (1999) [Pubmed]
  25. Mac-1 signaling via Src-family and Syk kinases results in elastase-dependent thrombohemorrhagic vasculopathy. Hirahashi, J., Mekala, D., Van Ziffle, J., Xiao, L., Saffaripour, S., Wagner, D.D., Shapiro, S.D., Lowell, C., Mayadas, T.N. Immunity (2006) [Pubmed]
  26. Blockade of attachment and fusion receptors inhibits HIV-1 infection of human cervical tissue. Hu, Q., Frank, I., Williams, V., Santos, J.J., Watts, P., Griffin, G.E., Moore, J.P., Pope, M., Shattock, R.J. J. Exp. Med. (2004) [Pubmed]
  27. Multiple beta 1 chain integrins are receptors for invasin, a protein that promotes bacterial penetration into mammalian cells. Isberg, R.R., Leong, J.M. Cell (1990) [Pubmed]
  28. A Role for p130Cas in Mechanotransduction. Geiger, B. Cell (2006) [Pubmed]
  29. Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Brooks, P.C., Montgomery, A.M., Rosenfeld, M., Reisfeld, R.A., Hu, T., Klier, G., Cheresh, D.A. Cell (1994) [Pubmed]
  30. Fibrillar collagen inhibits arterial smooth muscle proliferation through regulation of Cdk2 inhibitors. Koyama, H., Raines, E.W., Bornfeldt, K.E., Roberts, J.M., Ross, R. Cell (1996) [Pubmed]
  31. Functions of pulmonary epithelial integrins: from development to disease. Sheppard, D. Physiol. Rev. (2003) [Pubmed]
  32. Recognition of distinct adhesive sites on fibrinogen by related integrins on platelets and endothelial cells. Cheresh, D.A., Berliner, S.A., Vicente, V., Ruggeri, Z.M. Cell (1989) [Pubmed]
  33. Integrin alpha 2 beta 1 (VLA-2) mediates reorganization and contraction of collagen matrices by human cells. Schiro, J.A., Chan, B.M., Roswit, W.T., Kassner, P.D., Pentland, A.P., Hemler, M.E., Eisen, A.Z., Kupper, T.S. Cell (1991) [Pubmed]
  34. Tenascin interferes with fibronectin action. Chiquet-Ehrismann, R., Kalla, P., Pearson, C.A., Beck, K., Chiquet, M. Cell (1988) [Pubmed]
  35. p120-Catenin and p190RhoGAP Regulate Cell-Cell Adhesion by Coordinating Antagonism between Rac and Rho. Wildenberg, G.A., Dohn, M.R., Carnahan, R.H., Davis, M.A., Lobdell, N.A., Settleman, J., Reynolds, A.B. Cell (2006) [Pubmed]
  36. Structure of integrin, a glycoprotein involved in the transmembrane linkage between fibronectin and actin. Tamkun, J.W., DeSimone, D.W., Fonda, D., Patel, R.S., Buck, C., Horwitz, A.F., Hynes, R.O. Cell (1986) [Pubmed]
  37. Recognition of a bacterial adhesion by an integrin: macrophage CR3 (alpha M beta 2, CD11b/CD18) binds filamentous hemagglutinin of Bordetella pertussis. Relman, D., Tuomanen, E., Falkow, S., Golenbock, D.T., Saukkonen, K., Wright, S.D. Cell (1990) [Pubmed]
  38. Integrins mediate functional pre- and postsynaptic maturation at a hippocampal synapse. Chavis, P., Westbrook, G. Nature (2001) [Pubmed]
  39. (64)Cu-labeled tetrameric and octameric RGD peptides for small-animal PET of tumor alpha(v)beta(3) integrin expression. Li, Z.B., Cai, W., Cao, Q., Chen, K., Wu, Z., He, L., Chen, X. J. Nucl. Med. (2007) [Pubmed]
  40. Fer-mediated cortactin phosphorylation is associated with efficient fibroblast migration and is dependent on reactive oxygen species generation during integrin-mediated cell adhesion. Sangrar, W., Gao, Y., Scott, M., Truesdell, P., Greer, P.A. Mol. Cell. Biol. (2007) [Pubmed]
  41. Role of the beta-subunit arginine/lysine finger in integrin heterodimer formation and function. Gupta, V., Alonso, J.L., Sugimori, T., Essafi, M., Issafi, M., Xiong, J.P., Arnaout, M.A. J. Immunol. (2008) [Pubmed]
  42. Real-time analysis of conformation-sensitive antibody binding provides new insights into integrin conformational regulation. Chigaev, A., Waller, A., Amit, O., Halip, L., Bologa, C.G., Sklar, L.A. J. Biol. Chem. (2009) [Pubmed]
  43. Glucocorticoids increase alpha5 integrin expression and adhesion of synovial fibroblasts but inhibit ERK signaling, migration, and cartilage invasion. Lowin, T., Straub, R.H., Neumann, E., Bosserhoff, A., Vogel, C., Moissl, C., Anders, S., Müller-Ladner, U., Schedel, J. Arthritis Rheum. (2009) [Pubmed]
  44. Pharmacokinetically Stabilized Cystine Knot Peptides That Bind Alpha-v-Beta-6 Integrin with Single-Digit Nanomolar Affinities for Detection of Pancreatic Cancer. Kimura, R.H., Teed, R., Hackel, B.J., Pysz, M.A., Chuang, C.Z., Sathirachinda, A., Willmann, J.K., Gambhir, S.S. Clin. Cancer Res. (2012) [Pubmed]
  45. Alpha L beta 2 integrin/LFA-1 binding to ICAM-1 induced by cytohesin-1, a cytoplasmic regulatory molecule. Kolanus, W., Nagel, W., Schiller, B., Zeitlmann, L., Godar, S., Stockinger, H., Seed, B. Cell (1996) [Pubmed]
  46. Absence of integrin alpha 7 causes a novel form of muscular dystrophy. Mayer, U., Saher, G., Fässler, R., Bornemann, A., Echtermeyer, F., von der Mark, H., Miosge, N., Pöschl, E., von der Mark, K. Nat. Genet. (1997) [Pubmed]
  47. Mutations in the 180-kD bullous pemphigoid antigen (BPAG2), a hemidesmosomal transmembrane collagen (COL17A1), in generalized atrophic benign epidermolysis bullosa. McGrath, J.A., Gatalica, B., Christiano, A.M., Li, K., Owaribe, K., McMillan, J.R., Eady, R.A., Uitto, J. Nat. Genet. (1995) [Pubmed]
  48. TIMP-2 mediated inhibition of angiogenesis: an MMP-independent mechanism. Seo, D.W., Li, H., Guedez, L., Wingfield, P.T., Diaz, T., Salloum, R., Wei, B.Y., Stetler-Stevenson, W.G. Cell (2003) [Pubmed]
  49. Endothelial Lu/BCAM glycoproteins are novel ligands for red blood cell alpha4beta1 integrin: role in adhesion of sickle red blood cells to endothelial cells. El Nemer, W., Wautier, M.P., Rahuel, C., Gane, P., Hermand, P., Galactéros, F., Wautier, J.L., Cartron, J.P., Colin, Y., Le Van Kim, C. Blood (2007) [Pubmed]
  50. Numb controls integrin endocytosis for directional cell migration with aPKC and PAR-3. Nishimura, T., Kaibuchi, K. Dev. Cell (2007) [Pubmed]
  51. Activation signal transduction by beta1 integrin in T cells from patients with systemic lupus erythematosus. Nakayamada, S., Saito, K., Nakano, K., Tanaka, Y. Arthritis Rheum. (2007) [Pubmed]
  52. Crosstalk between the alpha2beta1 integrin and c-met/HGF-R regulates innate immunity. McCall-Culbreath, K.D., Li, Z., Zutter, M.M. Blood (2008) [Pubmed]
  53. Integrin alpha9beta1 mediates enhanced cell migration through nitric oxide synthase activity regulated by Src tyrosine kinase. Gupta, S.K., Vlahakis, N.E. J. Cell. Sci. (2009) [Pubmed]
  54. Beta8 integrin regulates neurogenesis and neurovascular homeostasis in the adult brain. Mobley, A.K., Tchaicha, J.H., Shin, J., Hossain, M.G., McCarty, J.H. J. Cell. Sci. (2009) [Pubmed]
  55. Coordinate integrin and c-Met signaling regulate Wnt gene expression during epithelial morphogenesis. Liu, Y., Chattopadhyay, N., Qin, S., Szekeres, C., Vasylyeva, T., Mahoney, Z.X., Taglienti, M., Bates, C.M., Chapman, H.A., Miner, J.H., Kreidberg, J.A. Development (2009) [Pubmed]
  56. The adaptor protein Shc couples a class of integrins to the control of cell cycle progression. Wary, K.K., Mainiero, F., Isakoff, S.J., Marcantonio, E.E., Giancotti, F.G. Cell (1996) [Pubmed]
  57. Extracellular matrix proteins protect small cell lung cancer cells against apoptosis: a mechanism for small cell lung cancer growth and drug resistance in vivo. Sethi, T., Rintoul, R.C., Moore, S.M., MacKinnon, A.C., Salter, D., Choo, C., Chilvers, E.R., Dransfield, I., Donnelly, S.C., Strieter, R., Haslett, C. Nat. Med. (1999) [Pubmed]
  58. Fibronectin and VLA-4 in haematopoietic stem cell-microenvironment interactions. Williams, D.A., Rios, M., Stephens, C., Patel, V.P. Nature (1991) [Pubmed]
  59. Integrin regulation of lymphocyte trafficking: lessons from structural and signaling studies. Kinashi, T. Adv. Immunol. (2007) [Pubmed]
 
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