integrins

Summary

Summary: A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors(RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.

Top Publications

  1. ncbi Integrins: bidirectional, allosteric signaling machines
    Richard O Hynes
    Howard Hughes Medical Institute, Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 110:673-87. 2002
  2. ncbi Cell migration: integrating signals from front to back
    Anne J Ridley
    Ludwig Institute for Cancer Research, Royal Free and University College School of Medicine, London W1W 7BS, UK
    Science 302:1704-9. 2003
  3. ncbi Integrins in cancer: biological implications and therapeutic opportunities
    Jay S Desgrosellier
    Department of Pathology, Moores University of California at San Diego Cancer Center, La Jolla, 92093 0803, United States
    Nat Rev Cancer 10:9-22. 2010
  4. ncbi Integrins as therapeutic targets
    Simon L Goodman
    Department of Cellular Pharmacology Oncology Platform, Merck KGaA, Frankfurterstrasse 250, 64271 Darmstadt, Germany
    Trends Pharmacol Sci 33:405-12. 2012
  5. pmc Integrins in cell migration
    Anna Huttenlocher
    Departments of Pediatrics and Medical Microbiology and Immunology, University of Wisconsin Madison, Madison, Wsconsin 53706, USA
    Cold Spring Harb Perspect Biol 3:a005074. 2011
  6. ncbi Retinoic acid imprints gut-homing specificity on T cells
    Makoto Iwata
    Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida shi, Tokyo 194 8511, Japan
    Immunity 21:527-38. 2004
  7. ncbi Taking cell-matrix adhesions to the third dimension
    E Cukierman
    Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    Science 294:1708-12. 2001
  8. ncbi Integrin signaling
    F G Giancotti
    Cellular Biochemistry and Biophysics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Science 285:1028-32. 1999
  9. pmc Integrins
    Malgorzata Barczyk
    Department of Biomedicine, University of Bergen, Norway
    Cell Tissue Res 339:269-80. 2010
  10. ncbi Role of integrins in cell invasion and migration
    John D Hood
    Scripps Research Institute, Departments of Immunology and Vascular Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Rev Cancer 2:91-100. 2002

Detail Information

Publications334 found, 100 shown here

  1. ncbi Integrins: bidirectional, allosteric signaling machines
    Richard O Hynes
    Howard Hughes Medical Institute, Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 110:673-87. 2002
    In their roles as major adhesion receptors, integrins signal across the plasma membrane in both directions...
  2. ncbi Cell migration: integrating signals from front to back
    Anne J Ridley
    Ludwig Institute for Cancer Research, Royal Free and University College School of Medicine, London W1W 7BS, UK
    Science 302:1704-9. 2003
    ....
  3. ncbi Integrins in cancer: biological implications and therapeutic opportunities
    Jay S Desgrosellier
    Department of Pathology, Moores University of California at San Diego Cancer Center, La Jolla, 92093 0803, United States
    Nat Rev Cancer 10:9-22. 2010
    ..The importance of integrins in several cell types that affect tumour progression has made them an appealing target for cancer therapy...
  4. ncbi Integrins as therapeutic targets
    Simon L Goodman
    Department of Cellular Pharmacology Oncology Platform, Merck KGaA, Frankfurterstrasse 250, 64271 Darmstadt, Germany
    Trends Pharmacol Sci 33:405-12. 2012
    b>Integrins are a large family of molecules that are central regulators in multicellular biology. They orchestrate cell-cell and cell-extracellular matrix (ECM) adhesive interactions from embryonic development to mature tissue function...
  5. pmc Integrins in cell migration
    Anna Huttenlocher
    Departments of Pediatrics and Medical Microbiology and Immunology, University of Wisconsin Madison, Madison, Wsconsin 53706, USA
    Cold Spring Harb Perspect Biol 3:a005074. 2011
    ..Finally, we address mechanisms of adhesion assembly and disassembly and the role of adhesion in cellular polarity...
  6. ncbi Retinoic acid imprints gut-homing specificity on T cells
    Makoto Iwata
    Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida shi, Tokyo 194 8511, Japan
    Immunity 21:527-38. 2004
    ..These findings revealed a novel role for retinoic acid in the imprinting of gut-homing specificity on T cells...
  7. ncbi Taking cell-matrix adhesions to the third dimension
    E Cukierman
    Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    Science 294:1708-12. 2001
    ..focal and fibrillar adhesions characterized on 2D substrates in their content of alpha5beta1 and alphavbeta3 integrins, paxillin, other cytoskeletal components, and tyrosine phosphorylation of focal adhesion kinase (FAK)...
  8. ncbi Integrin signaling
    F G Giancotti
    Cellular Biochemistry and Biophysics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Science 285:1028-32. 1999
    ..The ECM exerts profound control over cells. The effects of the matrix are primarily mediated by integrins, a family of cell surface receptors that attach cells to the matrix and mediate mechanical and chemical signals ..
  9. pmc Integrins
    Malgorzata Barczyk
    Department of Biomedicine, University of Bergen, Norway
    Cell Tissue Res 339:269-80. 2010
    b>Integrins are cell adhesion receptors that are evolutionary old and that play important roles during developmental and pathological processes...
  10. ncbi Role of integrins in cell invasion and migration
    John D Hood
    Scripps Research Institute, Departments of Immunology and Vascular Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Rev Cancer 2:91-100. 2002
    ..The attachment is mediated by cell-surface receptors known as integrins, which bind to components of the extracellular matrix...
  11. ncbi The tail of integrins, talin, and kindlins
    Markus Moser
    Max Planck Institute of Biochemistry, 82152 Martinsried, Germany
    Science 324:895-9. 2009
    b>Integrins are transmembrane cell-adhesion molecules that carry signals from the outside to the inside of the cell and vice versa...
  12. ncbi Adhesion signaling - crosstalk between integrins, Src and Rho
    Stephan Huveneers
    Division of Toxicology, Leiden Amsterdam Center for Drug Research, Leiden University, 2300 RA Leiden, The Netherlands
    J Cell Sci 122:1059-69. 2009
    ..b>Integrins sense the physical properties of the extracellular matrix and organize the cytoskeleton accordingly...
  13. pmc Integrin ligands at a glance
    Jonathan D Humphries
    Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK
    J Cell Sci 119:3901-3. 2006
  14. pmc The Rho GEFs LARG and GEF-H1 regulate the mechanical response to force on integrins
    Christophe Guilluy
    Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Nat Cell Biol 13:722-7. 2011
    ..The application of force on integrins triggers cytoskeletal rearrangements and growth of the associated adhesion complex, resulting in increased ..
  15. ncbi Integrins: masters and slaves of endocytic transport
    Patrick T Caswell
    Beatson Institute for Cancer Research, Cancer Research UK, Glasgow, G61 3BX, Scotland
    Nat Rev Mol Cell Biol 10:843-53. 2009
    ..in obtaining detailed descriptions of the molecular machinery responsible for internalizing and recycling integrins. New findings indicate that integrin trafficking dictates the nature of Rho GTPase signalling during cytokinesis ..
  16. ncbi Rapid leukocyte migration by integrin-independent flowing and squeezing
    Tim Lämmermann
    Department of Molecular Medicine, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany
    Nature 453:51-5. 2008
    ..As migration on two-dimensional substrates naturally overemphasizes the role of adhesion, the contribution of integrins during three-dimensional movement of leukocytes within tissues has remained controversial...
  17. pmc The final steps of integrin activation: the end game
    Sanford J Shattil
    Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
    Nat Rev Mol Cell Biol 11:288-300. 2010
    Cell-directed changes in the ligand-binding affinity ('activation') of integrins regulate cell adhesion and migration, extracellular matrix assembly and mechanotransduction, thereby contributing to embryonic development and diseases such ..
  18. pmc The C terminus of talin links integrins to cell cycle progression
    Pengbo Wang
    Wellcome Trust Centre for Cell Matrix Research, University of Manchester, Manchester M13 9PT, England, UK
    J Cell Biol 195:499-513. 2011
    b>Integrins are cell adhesion receptors that sense the extracellular matrix (ECM) environment...
  19. pmc Vinculin controls focal adhesion formation by direct interactions with talin and actin
    Jonathan D Humphries
    Wellcome Trust Centre for Cell Matrix Research, University of Manchester, Manchester M13 9PT, England, UK
    J Cell Biol 179:1043-57. 2007
    ..The vinculin tail, however, is responsible for the functional link of FAs to the actin cytoskeleton. We propose a new model that explains how vinculin orchestrates FAs...
  20. pmc Structural basis of integrin regulation and signaling
    Bing Hao Luo
    The CBR Institute for Biomedical Research, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Annu Rev Immunol 25:619-47. 2007
    b>Integrins are cell adhesion molecules that mediate cell-cell, cell-extracellular matrix, and cell-pathogen interactions...
  21. ncbi Requirement of vascular integrin alpha v beta 3 for angiogenesis
    P C Brooks
    Department of Immunology, Scripps Research Institute, La Jolla, CA 92037
    Science 264:569-71. 1994
    ..These findings suggest that alpha v beta 3 may be a useful therapeutic target for diseases characterized by neovascularization...
  22. pmc Functional atlas of the integrin adhesome
    Ronen Zaidel-Bar
    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel
    Nat Cell Biol 9:858-67. 2007
    ..We discuss the role of the different network modules in regulating the structural and signalling functions of cell-matrix adhesions...
  23. pmc Integrins in angiogenesis and lymphangiogenesis
    Christie J Avraamides
    Moores UCSD Cancer Center, 3, 855 Health Sciences Drive, La Jolla, California 92092 0819, USA
    Nat Rev Cancer 8:604-17. 2008
    ..Angiogenesis and lymphangiogenesis are regulated by integrins, which are members of a family of cell surface receptors whose ligands are extracellular matrix proteins and ..
  24. ncbi Unique and redundant functions of integrins in the epidermis
    Coert Margadant
    Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    FASEB J 24:4133-52. 2010
    ..Epidermal adhesion is mediated primarily by integrins, cell-surface receptors that connect the extracellular matrix to the cytoskeleton...
  25. ncbi Integrin signalling during tumour progression
    Wenjun Guo
    Cell Biology Program, Sloan Kettering Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, Weill Graduate School of Medical Sciences, Sloan Kettering Institute Cornell University, New York, New York, USA
    Nat Rev Mol Cell Biol 5:816-26. 2004
    ..There is increasing evidence that certain integrins associate with receptor tyrosine kinases (RTKs) to activate signalling pathways that are necessary for tumour ..
  26. ncbi HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells
    James Arthos
    Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Immunol 9:301-9. 2008
    ..On CD4+ T cells, engagement of alpha4beta7 by gp120 resulted in rapid activation of LFA-1, the central integrin involved in the establishment of virological synapses, which facilitate efficient cell-to-cell spreading of HIV-1...
  27. pmc The integrins
    Yoshikazu Takada
    Department of Dermatology, University of California Davis School of Medicine, Second Avenue, Sacramento, CA 95817, USA
    Genome Biol 8:215. 2007
    The integrins are a superfamily of cell adhesion receptors that bind to extracellular matrix ligands, cell-surface ligands, and soluble ligands...
  28. ncbi FAK integrates growth-factor and integrin signals to promote cell migration
    D J Sieg
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Nat Cell Biol 2:249-56. 2000
    ..Our results establish that FAK is an important receptor-proximal link between growth-factor-receptor and integrin signalling pathways...
  29. pmc The Par complex and integrins direct asymmetric cell division in adult intestinal stem cells
    Spyros Goulas
    Institute of Molecular Biotechnology of the Austrian Academy of Science IMBA, Dr Bohr Gasse 3, 1030 Vienna, Austria
    Cell Stem Cell 11:529-40. 2012
    ..Our data indicate that mechanisms for intrinsically asymmetric cell division can be adapted to allow for the flexibility in lineage decisions that is required in adult stem cells...
  30. ncbi The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis
    J S Munger
    Department of Medicine, and Kaplan Cancer Center, New York University School of Medicine, New York 10016 6402, USA
    Cell 96:319-28. 1999
    ..These data identify a novel mechanism for locally regulating TGF beta 1 function in vivo by regulating expression of the alpha v beta 6 integrin...
  31. ncbi Long-term self-renewal of human pluripotent stem cells on human recombinant laminin-511
    Sergey Rodin
    Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
    Nat Biotechnol 28:611-5. 2010
    ..This xeno-free and feeder-free system may be useful for the development of cell lineages for therapeutic purposes...
  32. ncbi Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization
    George E Davis
    Department of Pathology, Texas A and M University System Health Science Center, College Station, USA
    Circ Res 97:1093-107. 2005
    ..Thus, the composition of ECM and therefore the regulation of ECM degradation and remodeling serves pivotally in the control of lumen and tube formation and, finally, neovessel stability and maturation...
  33. ncbi Consequences of lack of beta 1 integrin gene expression in mice
    R Fassler
    Max Planck Institut fur Biochemie, Martinsried, Germany
    Genes Dev 9:1896-908. 1995
    beta 1 integrins are cell-surface receptors that mediate cell-cell and cell-matrix interactions. We have generated a null mutation in the gene for the beta 1 integrin subunit in mice and embryonic stem (ES) cells...
  34. ncbi The interplay between Src and integrins in normal and tumor biology
    Martin P Playford
    Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, NC 27599, USA
    Oncogene 23:7928-46. 2004
    ....
  35. ncbi Cell-matrix adhesion
    Allison L Berrier
    Katrina Visiting Faculty Program, National Center on Minority Health and Health Disparities, National Institutes of Health, Bethesda, Maryland, USA
    J Cell Physiol 213:565-73. 2007
    ..Many of these interactions involve transmembrane integrin receptors. Integrins cluster in specific cell-matrix adhesions to provide dynamic links between extracellular and intracellular ..
  36. pmc The integrin alpha(v)beta8 mediates epithelial homeostasis through MT1-MMP-dependent activation of TGF-beta1
    Dezhi Mu
    Department of Pathology, University of California at San Francisco Mt Zion Cancer Center, San Francisco, CA 94143, USA
    J Cell Biol 157:493-507. 2002
    b>Integrins, matrix metalloproteases (MMPs), and the cytokine TGF-beta have each been implicated in homeostatic cell behaviors such as cell growth and matrix remodeling...
  37. pmc Collagen fibrillogenesis: fibronectin, integrins, and minor collagens as organizers and nucleators
    Karl E Kadler
    Wellcome Trust Centre for Cell Matrix Research, University of Manchester, Faculty of Life Sciences, Michael Smith Building, Oxford Road, Manchester M13 9PT, United Kingdom
    Curr Opin Cell Biol 20:495-501. 2008
    ..I-containing fibrils do not form in the absence of fibronectin, fibronectin-binding and collagen-binding integrins, and collagen V...
  38. pmc The structure of an integrin/talin complex reveals the basis of inside-out signal transduction
    Nicholas J Anthis
    Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
    EMBO J 28:3623-32. 2009
    Fundamental to cell adhesion and migration, integrins are large heterodimeric membrane proteins that uniquely mediate inside-out signal transduction, whereby adhesion to the extracellular matrix is activated from within the cell by ..
  39. pmc The relationship between force and focal complex development
    Catherine G Galbraith
    Duke University Medical Center, Durham, NC 27710, USA
    J Cell Biol 159:695-705. 2002
    ..However, it is unclear if connections between integrins and the ECM are immediately capable of transducing cytoskeletal contraction into migration force, or whether ..
  40. ncbi The mechanical integrin cycle
    Eileen Puklin-Faucher
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    J Cell Sci 122:179-86. 2009
    ..As the major force-bearing adhesion-receptor protein, integrins have a central role in how cells sense and respond to the mechanics of their surroundings...
  41. ncbi Imaging of integrins as biomarkers for tumor angiogenesis
    Weibo Cai
    The Molecular Imaging Program at Stanford, Department of Radiology and Bio X Program, Stanford University School of Medicine, California, USA
    Curr Pharm Des 14:2943-73. 2008
    ..The design, optimization, and characterization of imaging agents targeting integrins will be presented and areas needing extensive future research effort will be discussed...
  42. pmc The pattern recognition receptor (RAGE) is a counterreceptor for leukocyte integrins: a novel pathway for inflammatory cell recruitment
    Triantafyllos Chavakis
    Department of Internal Medicine I, University Heidelberg, Bergheimer Strasse 58, D 69115 Heidelberg, Germany
    J Exp Med 198:1507-15. 2003
    ..of RAGE with the beta2-integrin Mac-1 and, to a lower extent, with p150,95 but not with LFA-1 or with beta1-integrins. The RAGE-Mac-1 interaction was augmented by the proinflammatory RAGE-ligand, S100-protein...
  43. ncbi Complexes of tetraspanins with integrins: more than meets the eye
    F Berditchevski
    CRC Institute for Cancer Studies, The University of Birmingham, Edgbaston, Birmingham, B15 2TA, UK
    J Cell Sci 114:4143-51. 2001
    ..A substantial fraction of tetraspanins colocalise with integrins in various intracellular vesicular compartments...
  44. ncbi Periostin secreted by epithelial ovarian carcinoma is a ligand for alpha(V)beta(3) and alpha(V)beta(5) integrins and promotes cell motility
    Lindsay Gillan
    Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
    Cancer Res 62:5358-64. 2002
    ..Furthermore, alpha(V)beta(3) integrin, but not beta(1) integrins, colocalizes to the focal adhesion plaques formed on PN...
  45. pmc Beta3-integrin-deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival
    K M Hodivala-Dilke
    Howard Hughes Medical Institute, Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Clin Invest 103:229-38. 1999
    beta3 integrins have been implicated in a wide variety of functions, including platelet aggregation and thrombosis (alphaIIbbeta3) and implantation, placentation, angiogenesis, bone remodeling, and tumor progression (alphavbeta3)...
  46. ncbi Structural basis of collagen recognition by integrin alpha2beta1
    J Emsley
    Department of Biochemistry, University of Leicester, United Kingdom
    Cell 101:47-56. 2000
    ..The structural features observed here may represent a general mechanism for integrin-ligand recognition...
  47. pmc Small intestinal CD103+ dendritic cells display unique functional properties that are conserved between mice and humans
    Elin Jaensson
    Immunology Section, BMC D14, 221 84 Lund University, Lund, Sweden
    J Exp Med 205:2139-49. 2008
    ..Thus, small intestinal CD103(+) DCs represent a potential novel target for regulating human intestinal inflammatory responses...
  48. ncbi Adhesion receptors of the immune system
    T A Springer
    Department of Pathology, Harvard Medical School, Boston, Massachusetts
    Nature 346:425-34. 1990
    ..Three families of cell-surface molecules regulate the migration of lymphocytes and the interactions of activated cells during immune responses...
  49. pmc Role of integrins in regulating epidermal adhesion, growth and differentiation
    Fiona M Watt
    Cancer Research UK, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    EMBO J 21:3919-26. 2002
    ..expression is altered when the epidermis is damaged or diseased, and there is good evidence that specific integrins can contribute positively or negatively to pathogenesis...
  50. ncbi Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN
    M Tamura
    Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892 4370, USA
    Science 280:1614-7. 1998
    ..Overexpression of FAK partially antagonized the effects of PTEN. Thus, PTEN phosphatase may function as a tumor suppressor by negatively regulating cell interactions with the extracellular matrix...
  51. ncbi Tetraspanins
    C Boucheix
    INSERM U268, Institut Andre Lwoff, Hĵpital Paul Brousse, Villejuif, France
    Cell Mol Life Sci 58:1189-205. 2001
    ..properties is their ability to form a network of multimolecular complexes, the 'tetraspanin web', in which integrins are included...
  52. ncbi Cooperation between integrins and growth factor receptors in signaling and endocytosis
    Johanna Ivaska
    Medical Biotechnology, VTT Technical Research Center of Finland, Turku FI 20520, Finland
    Annu Rev Cell Dev Biol 27:291-320. 2011
    ..b>Integrins can directly bind to GFs and promote their activation...
  53. pmc Cartilage oligomeric matrix protein/thrombospondin 5 supports chondrocyte attachment through interaction with integrins
    Faye Hui Chen
    Department of Orthopaedic Surgery, Columbia University, New York, New York 10032, USA
    J Biol Chem 280:32655-61. 2005
    ..The interactions of COMP/TSP5 with the integrins are dependent on COMP/TSP5 conformation...
  54. ncbi Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells
    J Rodrigo Mora
    The Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 424:88-93. 2003
    ..These findings establish that Peyer's patch dendritic cells imprint gut-homing specificity on T cells, and thus license effector/memory cells to access anatomical sites most likely to contain their cognate antigen...
  55. pmc Cell spreading and focal adhesion dynamics are regulated by spacing of integrin ligands
    Elisabetta Ada Cavalcanti-Adam
    Max Planck Institute for Metals Research, Department of New Materials and Biosystems, Stuttgart, Germany
    Biophys J 92:2964-74. 2007
    ..By varying the spacing between the dots, we modulated the clustering of the associated integrins. We show that cell-surface attachment is not sensitive to pattern density, whereas the formation of stable focal ..
  56. ncbi Positional control of cell fate through joint integrin/receptor protein kinase signaling
    Filippo G Giancotti
    Cellular Biochemistry and Biophysics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Annu Rev Cell Dev Biol 19:173-206. 2003
    ..The integrins are a large family of receptors that attach cells to the matrix, organize their cytoskeleton, and cooperate with ..
  57. pmc Integrins and extracellular matrix in mechanotransduction
    Martin Alexander Schwartz
    Departments of Microbiology, Cell Biology, and Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22908, USA
    Cold Spring Harb Perspect Biol 2:a005066. 2010
    b>Integrins bind extracellular matrix fibrils and associate with intracellular actin filaments through a variety of cytoskeletal linker proteins to mechanically connect intracellular and extracellular structures...
  58. pmc Rap1 translates chemokine signals to integrin activation, cell polarization, and motility across vascular endothelium under flow
    Mika Shimonaka
    Bayer Chair, Dept of Molecular Immunology and Allergy, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
    J Cell Biol 161:417-27. 2003
    ..Spa1 effectively suppressed this polarization after SLC treatment. This unique characteristic of Rap1 may control chemokine-induced lymphocyte extravasation...
  59. ncbi The integrin-growth factor receptor duet
    Naved Alam
    Department of Cancer Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    J Cell Physiol 213:649-53. 2007
    Cell adhesion receptors, referred to as integrins, are recognized as key regulators of cellular processes including growth and differentiation...
  60. ncbi Integrin-regulated FAK-Src signaling in normal and cancer cells
    Satyajit K Mitra
    The Scripps Research Institute, Department of Immunology, IMM21 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
    Curr Opin Cell Biol 18:516-23. 2006
    b>Integrins can alter cellular behavior through the recruitment and activation of signaling proteins such as non-receptor tyrosine kinases including focal adhesion kinase (FAK) and c-Src that form a dual kinase complex...
  61. pmc Beta1 integrin inhibitory antibody induces apoptosis of breast cancer cells, inhibits growth, and distinguishes malignant from normal phenotype in three dimensional cultures and in vivo
    Catherine C Park
    Departments of Radiation Oncology and Pathology, University of California San Francisco Mt Zion Cancer Center, 1600 Divisadero Street, San Francisco, CA 94143 1708, USA
    Cancer Res 66:1526-35. 2006
    ..Our findings indicate that beta(1) integrin is a promising therapeutic target, and that the three-dimensional lrECM culture assay can be used to effectively distinguish malignant and normal tissue response to therapy...
  62. ncbi Integrins: the keys to unlocking angiogenesis
    Rita Silva
    Adhesion and Angiogenesis Group, Centre for Tumour Biology, Cancer Research UK Clinical Centre, Institute of Cancer, Barts and The London and Queen Mary s School of Medicine and Dentistry, John Vane Science Centre, Charterhouse Square, London UK
    Arterioscler Thromb Vasc Biol 28:1703-13. 2008
    ..b>Integrins are cell adhesion molecules that are expressed on the surface of endothelial cells and pericytes, making them ..
  63. pmc The integrin alpha4beta7 forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1
    Claudia Cicala
    Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 106:20877-82. 2009
    ..The specific affinity of gp120 for alpha(4)beta(7) provides a mechanism for HIV-1 to target activated cells that are critical for efficient virus propagation and dissemination following sexual transmission...
  64. pmc Activation of integrins in endothelial cells by fluid shear stress mediates Rho-dependent cytoskeletal alignment
    E Tzima
    Department of Vascular Biology, The Scripps Research Institute, 10550 N.Torrey Pines Road, La Jolla, CA 92037, USA
    EMBO J 20:4639-47. 2001
    Fluid shear stress is a critical determinant of vascular remodeling and atherogenesis. Both integrins and the small GTPase Rho are implicated in endothelial cell responses to shear but the mechanisms are poorly understood...
  65. ncbi Paxillin and focal adhesion signalling
    C E Turner
    Department of Cell and Developmental Biology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, New York 13210, USA
    Nat Cell Biol 2:E231-6. 2000
    ..Paxillin is a multi-domain adaptor found at the interface between the plasma membrane and the actin cytoskeleton. Here it provides a platform for the integration and processing of adhesion- and growth factor-related signals...
  66. ncbi Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase
    Ellen J Ezratty
    Department of Anatomy and Cell Biology, Columbia University, 630 West 168th Street, BB 1217, New York, NY 10032, USA
    Nat Cell Biol 7:581-90. 2005
    ..Inhibition of dynamin prevents migration of cells with a focal adhesion phenotype. Our results show that focal adhesion disassembly involves microtubules, dynamin and FAK, and is not simply the reversal of focal adhesion formation...
  67. ncbi Integrins and the activation of latent transforming growth factor beta1 - an intimate relationship
    Pierre Jean Wipff
    Laboratory of Cell Biophysics, Bâtiment SG AA B143, Ecole Polytechnique Federale de Lausanne, CH 1015 Lausanne, Switzerland
    Eur J Cell Biol 87:601-15. 2008
    b>Integrins are crucial for the ability of cells to sense mechanical perturbations and to transmit intracellular stress to their environment...
  68. ncbi The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34(+) cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice
    A Peled
    Departments of Immunology and Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel
    Blood 95:3289-96. 2000
    ..of nonobese/severe combined immunodeficiency (NOD/SCID) mice by human stem cells is dependent on the major integrins very late activation antigen-4 (VLA-4); VLA-5; and to a lesser degree, lymphocyte function associated antigen-1 (..
  69. ncbi Severely reduced female fertility in CD9-deficient mice
    F Le Naour
    Institut National de la Sante et de la Recherche Medicale INSERM, Unité 268, Hopital Paul Brousse, 94800 Villejuif, France
    Science 287:319-21. 2000
    ..and CD63 are involved in metastasis suppression, an effect that may be related to their association with beta1 integrins. Knockout mice lacking CD9 were created to evaluate the physiological importance of CD9...
  70. pmc Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans
    Joan C Marini
    Bone and Extracellular Matrix Branch, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892, USA
    Hum Mutat 28:209-21. 2007
    ..with major ligand binding regions (MLBRs), suggesting crucial interactions of collagen monomers or fibrils with integrins, matrix metalloproteinases (MMPs), fibronectin, and cartilage oligomeric matrix protein (COMP)...
  71. pmc Integrin-dependent actomyosin contraction regulates epithelial cell scattering
    Johan de Rooij
    Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Cell Biol 171:153-64. 2005
    ..is enhanced on collagen and fibronectin, as compared with laminin1, suggesting possible cross talk between integrins and cell-cell junctions...
  72. ncbi Integrins in immunity
    Rachel Evans
    Leukocyte Adhesion Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    J Cell Sci 122:215-25. 2009
    ..the same biological rules as many other cell types, and this holds true particularly for the functioning of the integrins on these cells...
  73. ncbi Evaluation of prototype transmembrane 4 superfamily protein complexes and their relation to lipid rafts
    C Claas
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 276:7974-84. 2001
    ....
  74. ncbi Thrombin-cleaved osteopontin regulates hemopoietic stem and progenitor cell functions through interactions with alpha9beta1 and alpha4beta1 integrins
    Jochen Grassinger
    Australian Stem Cell Centre, Clayton, Australia
    Blood 114:49-59. 2009
    ..The N-terminal thrombin cleavage fragment of OPN through its binding to the alpha(9)beta(1) and alpha(4)beta(1) integrins plays a key role in the attraction, retention, regulation, and release of hemopoietic stem and progenitor cells ..
  75. pmc Cellular entry of hantaviruses which cause hemorrhagic fever with renal syndrome is mediated by beta3 integrins
    I N Gavrilovskaya
    Department of Medicine, State University of New York at Stony Brook, Stony Brook, New York 11794, USA
    J Virol 73:3951-9. 1999
    ..this report, we demonstrate that the cellular entry of HFRS-associated hantaviruses is facilitated by specific integrins expressed on platelets, endothelial cells, and macrophages...
  76. ncbi Deletion of beta 1 integrins in mice results in inner cell mass failure and peri-implantation lethality
    L E Stephens
    Department of Stomatology, University of California, San Francisco 94143 0512, USA
    Genes Dev 9:1883-95. 1995
    ..To determine when beta 1 integrins become critical during embryonic development, we generated mutant mice with a targeted disruption of the beta 1 ..
  77. ncbi Dissecting the molecular architecture of integrin adhesion sites by cryo-electron tomography
    Israel Patla
    Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben Gurion University of the Negev, Be er Sheva 84120, Israel
    Nat Cell Biol 12:909-15. 2010
    ..Our findings clarify the internal architecture of focal adhesions at molecular resolution, and provide insights into their scaffolding and mechanosensory functions...
  78. ncbi Signal co-operation between integrins and other receptor systems
    Charles H Streuli
    Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, U K
    Biochem J 418:491-506. 2009
    ..In the present review we explore how one class of adhesion receptor, the integrins, co-operate with other types of receptor to control diverse aspects of cell fate...
  79. ncbi Integrin activation
    David A Calderwood
    Department of Pharmacology, Yale University School of Medicine, Sterling Hall of Medicine, New Haven, CT 06520, USA
    J Cell Sci 117:657-66. 2004
    ..Recent studies have shed light on the final intracellular steps in this process and have revealed a vital role for the cytoskeletal protein talin...
  80. pmc Small integrin-binding ligand N-linked glycoproteins (SIBLINGs): multifunctional proteins in cancer
    Akeila Bellahcene
    Metastasis Research Laboratory, University of Liege, Tour de Pathologie, 1, Bat B23, Sart Tilman via 4000 Liege, Belgium
    Nat Rev Cancer 8:212-26. 2008
    ....
  81. pmc The genotype of early-transmitting HIV gp120s promotes α (4) β(7)-reactivity, revealing α (4) β(7) +/CD4+ T cells as key targets in mucosal transmission
    Fatima Nawaz
    Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS Pathog 7:e1001301. 2011
    ..Understanding the structural features that characterize early-transmitting gp120s may aid in the design of an effective gp120-based subunit vaccine...
  82. pmc Conditional ablation of beta1 integrin in skin. Severe defects in epidermal proliferation, basement membrane formation, and hair follicle invagination
    S Raghavan
    Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, Illinois 60637, USA
    J Cell Biol 150:1149-60. 2000
    The major epidermal integrins are alpha3beta1 and hemidesmosome-specific alpha6beta4; both share laminin 5 as ligand...
  83. pmc Structure and mechanics of integrin-based cell adhesion
    M Amin Arnaout
    Nephrology Division, Leukocyte Biology and Inflammation Program, Structural Biology Program, Massachusetts General Hospital, and Harvard Medical School, 149 13th Street, Charlestown, MA 02129, United States
    Curr Opin Cell Biol 19:495-507. 2007
    b>Integrins are alpha/beta heterodimeric adhesion glycoprotein receptors that regulate a wide variety of dynamic cellular processes such as cell migration, phagocytosis, and growth and development...
  84. pmc Integrins: roles in cancer development and as treatment targets
    H Jin
    John and Rebecca Moores Comprehensive Cancer Center, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0912, USA
    Br J Cancer 90:561-5. 2004
    ..Several integrins play key roles in promoting tumour angiogenesis and tumour metastasis...
  85. pmc Extracellular matrix: a gatekeeper in the transition from dormancy to metastatic growth
    Dalit Barkan
    Department of Biology, Faculty of Sciences, Haifa University, Haifa, Israel
    Eur J Cancer 46:1181-8. 2010
    ..The roles of integrins, fibronectin, and collagen are discussed, as are factors that can change the ECM...
  86. ncbi Rap1: a turnabout for the crosstalk between cadherins and integrins
    Saverio Francesco Retta
    Department of Genetics, Biology and Biochemistry, University of Torino, Via Santena 5 bis, I 10126 Torino, Italy
    Eur J Cell Biol 85:283-93. 2006
    The coordinate modulation of the cellular functions of cadherins and integrins plays an essential role in fundamental physiological and pathological processes, including morphogenesis, tissue differentiation and renewal, wound healing, ..
  87. ncbi Integrins in mechanotransduction
    Akira Katsumi
    Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA
    J Biol Chem 279:12001-4. 2004
    ..Integrin-mediated adhesions are intrinsically mechanosensitive and a large body of data implicates integrins in sensing mechanical forces...
  88. ncbi Fibronectin at a glance
    Roumen Pankov
    Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Sci 115:3861-3. 2002
  89. ncbi The role of integrin binding sites in fibronectin matrix assembly in vivo
    Michael Leiss
    Max Planck Institute of Biochemistry, Department of Molecular Medicine, 82152 Martinsried, Germany
    Curr Opin Cell Biol 20:502-7. 2008
    ..Fibrillogenesis is initiated and governed by cell surface integrins that bind to specific sites in the FN molecule...
  90. ncbi Important role of integrins in the cancer biology
    R Rathinam
    Department of Biochemistry and Molecular Biology, Stanley S Scott Cancer Center, LSU School of Medicine, 1901 Perdido Street, New Orleans, LA, 70112, USA
    Cancer Metastasis Rev 29:223-37. 2010
    Adhesion of breast cancer cells is supported by various integrins. Cell adhesion is critical for maintenance of both three-dimensional and normal function of these tissues...
  91. pmc Vascular endothelial growth factor A (VEGF-A) induces endothelial and cancer cell migration through direct binding to integrin {alpha}9{beta}1: identification of a specific {alpha}9{beta}1 binding site
    Saji Oommen
    Thoracic Disease Research Unit, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Biol Chem 286:1083-92. 2011
    ..This interaction is biologically important because it mediates in vitro endothelial cell tube formation, wound healing, and cancer cell invasion. These novel findings identify EYP as a potential site for directed pharmacotherapy...
  92. ncbi Structural basis for ligand recognition by integrins
    Junichi Takagi
    Laboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, 3 2 Yamadaoka, Suita, Osaka 565 0871, Japan
    Curr Opin Cell Biol 19:557-64. 2007
    b>Integrins, the major cell surface receptors mediating cell-extracellular matrix (ECM) adhesion, are central to the basic physiology underlying all multicellular organisms...
  93. pmc Integrins and cell-fate determination
    Charles H Streuli
    Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK
    J Cell Sci 122:171-7. 2009
    All cellular processes are determined by adhesive interactions between cells and their local microenvironment. Integrins, which constitute one class of cell-adhesion receptor, are multifunctional proteins that link cells to the ..
  94. pmc Synergistic control of cell adhesion by integrins and syndecans
    Mark R Morgan
    Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK
    Nat Rev Mol Cell Biol 8:957-69. 2007
    ..The integrins and the syndecans are two adhesion receptor families that mediate adhesion, but their relative and functional ..
  95. ncbi A novel, tissue-specific integrin subunit, beta nu, expressed in the midgut of Drosophila melanogaster
    G H Yee
    Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139
    Development 118:845-58. 1993
    The integrins are a family of cell surface receptors for extracellular matrix proteins and counter-receptors on other cells...
  96. pmc Fatal bilateral chylothorax in mice lacking the integrin alpha9beta1
    X Z Huang
    Lung Biology Center, Center for Occupational and Environmental Health, Cardiovascular Research Institute, San Francisco, California 94143 0854, USA
    Mol Cell Biol 20:5208-15. 2000
    ..Our results suggest that the alpha9 integrin is required for the normal development of the lymphatic system, including the thoracic duct, and that alpha9 deficiency could be one cause of congenital chylothorax...
  97. pmc Focal adhesion disassembly requires clathrin-dependent endocytosis of integrins
    Wei Ting Chao
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, 1 Baylor Plaza, BCM335, RM T419, Houston, TX 77030, USA
    FEBS Lett 583:1337-43. 2009
    ..show that adhesion turnover is mediated through dynamin- and clathrin-dependent endocytosis of activated beta1 integrins. Consistent with this, clathrin and the clathrin adaptors AP-2 and disabled-2 (DAB2) distribute along with ..
  98. ncbi Integrins and anoikis
    S M Frisch
    Burnham Institute, La Jolla Cancer Research Center, CA 92037, USA
    Curr Opin Cell Biol 9:701-6. 1997
    ..Focal adhesion kinase, when activated by integrins, can suppress anoikis...
  99. pmc The lymphangiogenic vascular endothelial growth factors VEGF-C and -D are ligands for the integrin alpha9beta1
    Nicholas E Vlahakis
    Lung Biology Center, University of California San Francisco, San Francisco, California, 94143 2922, USA
    J Biol Chem 280:4544-52. 2005
    ..The interaction between alpha9beta1 and VEGF-C and/or -D may begin to explain the abnormal lymphatic phenotype of the alpha9 knock-out mice...
  100. ncbi Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1
    C Berlin
    Department of Pathology, Stanford University, California 94305
    Cell 74:185-95. 1993
    ..Alpha 4 beta 7 can also bind VCAM-1, but this requires greater integrin activation than binding to MAdCAM-1. The findings imply a selective role for the interaction of alpha 4 beta 7 and MAdCAM-1 lymphocyte in homing to mucosal sites...
  101. ncbi Regulation of integrin function by the urokinase receptor
    Y Wei
    Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Science 273:1551-5. 1996
    ..The urokinase-type plasminogen activator receptor (uPAR) and integrins formed stable complexes that both inhibited native integrin adhesive function and promoted adhesion to ..

Research Grants72

  1. BETA 1 INTEGRIN ANTAGONISM & RETINAL NEOVASCULARIZATION
    DONALD SENGER; Fiscal Year: 2001
    ..VEGF markedly induces expression of the alpha-1-beta-1, alpha-2-beta-1, and alpha- 5-beta-3 cell surface integrins in dermal microvascular endothelial cells (ECs), and antagonism of alpha-1-beta-1, alpha-2-beta-1, and alpha-5 ..
  2. Regulation of mural cells during pulmonary capillary formation
    Stephen E McGowan; Fiscal Year: 2013
    ..Detailed time-lapse microscopic studies will reveal how laminin and integrins promote PDGF-A or PDGF-B-stimulated migration of fibroblasts and pericytes...
  3. Role of Peroxidasin in Glomerular Matrix Homeostasis
    Gautam Bhave; Fiscal Year: 2013
    ..Dr. Zent heads a well-funded group studying renal development and integrins and will provide expertise in the investigation of peroxidasin and cell-matrix interactions. Taken together, Dr...
  4. Interplay Between Tissue Architecture and Nuclear Organization in the DNA Damage
    Pierre Alexandre Vidi; Fiscal Year: 2013
    ..that the DDR is enhanced in polarized tissues by basement membrane (BM) signaling through hemidesmosomal integrins. This effect is observed both for non-neoplastic and malignant cells in 3D culture, but not in flat cell ..
  5. RSK-2 regulates integrin-mediated adhesion and migration
    JOE WILLIAM RAMOS; Fiscal Year: 2013
    ..2) Determine the functional consequences of RSK2 regulation of integrin activity. Integrins are involved in cell adhesion, migration, fibronectin matrix assembly and signal transduction...
  6. Integrin Regulation of Stretch-Activated Myometrial Signaling During Pregnancy an
    Heather R Burkin; Fiscal Year: 2013
    ..Because integrins have been shown to play pivotal roles in smooth muscle contractility, I hypothesize at least one integrin ..
  7. Integrin Regulation of Stretch-Activated Myometrial Signaling During Pregnancy an
    Heather R Burkin; Fiscal Year: 2012
    ..Because integrins have been shown to play pivotal roles in smooth muscle contractility, I hypothesize at least one integrin ..
  8. The Regulation of Salivary Gland Regeneration by P2Y2 Nucleotide Receptors
    GARY ANDREW WEISMAN; Fiscal Year: 2013
    ..interactions with complex signaling networks known to regulate cell growth and differentiation involving integrins, growth factor receptors, matrix metalloproteases, adhesion molecules and cytoskeletal proteins...
  9. Genetic Analysis of FAK Activity
    David D Schlaepfer; Fiscal Year: 2012
    ..Analysis of FAK Activity Binding interactions between extracellular matrix proteins such as fibronectin and integrins play fundamental roles during development by controlling cell adhesion, motility, and survival...
  10. Regulation of Fibronectin Matrix Assembly by uPAR
    PAULA J MC KEOWN-LONGO; Fiscal Year: 2012
    ..The roles of uPAR co-receptors in the activation of Src/EGFR (integrins, growth factor receptors and FPRL1) will be addressed using a combination of pharmacological inhibitors, gene ..
  11. Novel Chaperone Mechanism for Platelet Disorder
    Zihai Li; Fiscal Year: 2010
    ..By generating conditional gp96 null mice, we have found that gp96 is an essential chaperone for multiple integrins and Toll-like receptors (TLRs)...
  12. Periostin Regulation of Lung Fibrosis
    Bethany B Moore; Fiscal Year: 2013
    ..Blockade of periostin interactions with the avb3 and avb5 integrins via the administration of the OC-20 monoclonal Ab could partially reverse periostin-mediated wound closure and ..
  13. Thrombospondin 4 A1
    JOHN W LAWLER; Fiscal Year: 2010
    ..We have found that COMP binds to aggrecan, as well as to integrins in chondrocytes and fibroblasts...
  14. cGMP-dependent Protein Kinase Function in Osteoblast Mechanotransduction
    Renate B Pilz; Fiscal Year: 2013
    ..site), which required the protein tyrosine phosphatases (PTP) Shp-1 and -2, and cell attachment through $3 integrins. PKG II, Src, and Shp-2 co-localized with $3 in focal adhesion complexes in FSS-stimulated osteoblasts, and PKG ..
  15. Pathogenesis of autoimmune endocarditis: roles for Fc receptors and integrins?
    Bryce Binstadt; Fiscal Year: 2012
    ..The current proposal investigates how two families of innate immune receptors, Fc receptors and 22 integrins, contribute to the development of autoimmune endocarditis...
  16. Identification of Mechanoresponsive Promoter Elements in Chondrogenesis
    Dominik R Haudenschild; Fiscal Year: 2013
    ..These approaches have successfully identi- fied integrins, focal adhesion complexes, the cytoskeleton, and select kinase pathways as me- diators of mechanotransduction...
  17. Role of Integrins in Bladder Urothelium
    Warren G Hill; Fiscal Year: 2013
    DESCRIPTION: Integrins are a broad family of cell surface adhesion and signaling molecules which link the extracellular matrix (ECM) to the cytoskeleton of the cell...
  18. Inhibition of angiogenesis by thrombospondin-1 (A2)
    JOHN W LAWLER; Fiscal Year: 2012
    ..We have found that CD36 associates with vascular endothelial cell growth factor receptor 2 (VEGFR2), integrins, tetraspanins and their associated signal transduction molecules...
  19. MOLECULAR MODELS OF IMMUNE-MEDIATED VASCULAR INJURY
    Jeffrey R Bender; Fiscal Year: 2012
    ..including trafficking of host leukocytes into the graft, costimulation of alloreactive T cells through leukocyte integrins, or directed killing of donor target cells by conjugate formation with cytotoxic, allospecific effector cells...
  20. Extracellular Matrix Remodeling During Aging
    JANE M SOTTILE; Fiscal Year: 2010
    ..turnover occurs through endocytosis and intracellular degradation, and is regulated by both caveolin-1 and 21 integrins. Age-related decreases in caveolae, and in caveolae and clathrin-mediated endocytosis have been documented in ..
  21. ANDV Induced Responses of Hypoxic Endothelial Cells
    Erich R Mackow; Fiscal Year: 2012
    ..molecule-1 (PECAM-1) and PECAM-1: 1) is activated by VEGF, 2) negatively regulates the activation of platelet integrins and 3) stimulates prostacyclin release from ECs...
  22. Role of Focal Adhesion Kinase (FAK) in Nephrosis and Nephritis
    Shuta Ishibe; Fiscal Year: 2013
    ..between the glomerular basement membrane and the extracellular matrix, which is comprised of focal adhesions and integrins. The goal of this research project is to define the role of focal adhesion protein, Focal Adhesion Kinase (FAK), ..
  23. Regulatory Mechanisms of Oxidative Stress in Cardiac Angiogenesis Postinfarction
    Yao Sun; Fiscal Year: 2013
    ..cells to detach and migrate into the infarcted myocardium;and 2) ROS stimulate the expression of angiogenic integrins, thereby activating the integrin signaling pathway and promoting endothelial cell adhesion and migration...
  24. Plexin signalling in melanocyte biology and melanoma progression
    Glynis A Scott; Fiscal Year: 2013
    ..through stimulation of intracellular signaling pathways that include the GTP binding proteins Ras, Rho, Rac, integrins and LIM kinase- cofilin pathways...
  25. Distinct roles of CARP target genes in wound healing
    Karinna Almodóvar; Fiscal Year: 2013
    ..Thus, interaction and crosstalk between cells, MMPs, integrins, and other players determines remodeling and vascularization during wound healing...
  26. Signaling of Integrin Alpha 7
    Jianhua Luo; Fiscal Year: 2009
    ..Interestingly, we also found that ILK, a serine/threonine kinase and structural protein associated with integrins and the cytoskeleton, bound and phosphorylated a tumor suppressor gene called myopodin, which regulates cell ..
  27. Signaling of Integrin Alpha 7
    Jianhua Luo; Fiscal Year: 2013
    ..Interestingly, we also found that ILK, a serine/threonine kinase and structural protein associated with integrins and the cytoskeleton, bound and phosphorlyated a tumor suppressor gene called myopodin, which regulates cell ..
  28. Role of Nox4 in VSMC Migration
    MAZEN KHALIL KHALIL; Fiscal Year: 2011
    ..Migration is a finely orchestrated process that involves the interaction of the extracellular matrix (ECM), integrins, cytoskeletal proteins and NADPH oxidases (Noxes)...
  29. Analysis of alphaVbeta8 Integrin In Gliomagenesis
    Joseph H McCarty; Fiscal Year: 2012
    ..In this project we will study how cell adhesion molecules, known as integrins, regulate the onset and progression of gliomas in mice and humans...
  30. Regulation of Osteoblast Function by Megakaryocytes: Key Signaling Proteins
    Melissa A Kacena; Fiscal Year: 2013
    ..of the proline-rich tyrosine kinase 2 (Pyk2), a key protein kinase involved in signaling downstream of activated integrins, and that Pyk2 forms a complex with Rb and Mdm2...
  31. Regulation and Function of the Matricellular Protein CCN1 in Ischemic Retinopathy
    Brahim Chaqour; Fiscal Year: 2013
    ..In vitro data showed that CCN1 functions primarily through direct binding to specific integrins and ECM proteins, and/or indirectly through modulation of growth factor and Wnt protein expression and/or ..
  32. Interaction of thrombospondin-1 with alpha9beta1 integrin in glioma angiogenesis
    Cezary Marcinkiewicz; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Previous studies revealed that certain integrins expressed on endothelial cells play a significant role in the progression of angiogenesis and are an attractive target for the development of ..
  33. Fetal HCMV Infection: Role of the Human Placenta
    LENORE PALMA PEREIRA; Fiscal Year: 2013
    ..Aim 1. Study direct HCMV infection of decidual LEC to identify molecular pathways that dysregulate integrins that function as downstream effectors of chemotaxis, migration and cord formation. Aim 2...
  34. Integrin-dependent mechanism of T cell-mediated pulmonary fibrosis
    Irina G Luzina; Fiscal Year: 2012
    ..Data suggest that T cells are commonly present in the lungs of patients in association with fibrosis and express integrins, and that these integrins may be a master switch that defines a profibrotic or antifibrotic phenotype of T cells...
  35. Long-lived B cell Immunity in the Respiratory Tract
    Nicole Baumgarth; Fiscal Year: 2013
    ..lung tissue plasma cell pools, and using genetic screening and a custom microfluidics device, will identify the integrins and chemokines/receptors responsible for the selective accumulation and/or retention of plasma cells the lung ..
  36. An angiogenic role for the alpha 5 beta 1 and alpha V beta 3 integrins during cer
    D RICHARD MILNER; Fiscal Year: 2012
    ..is that cerebral ischemia induces brain endothelial cell expression of the a5[unreadable]1 and av[unreadable]3 integrins, and that fibronectin promotes cerebral angiogenesis, via these integrins...
  37. Cell Models for Alzheimer's disease (AD): Lipids and Related Signaling Pathways
    Grace Y Sun; Fiscal Year: 2012
    ..P2Y2Rs) for cytokine-like nucleotides in astrocytes and cerebral microvessels through transactivation of integrins and growth factor receptors, and P2Y2Rs mediate neuroprotective APP processing by a different pathway than ..
  38. HTS platform for identification of regulators of cell adhesion molecule signaling
    Darren G Woodside; Fiscal Year: 2013
    ..There is need for a new strategy to target integrins that would eliminate side-effects...
  39. EXTRACELLULAR MATRIX IN INFLAMMATORY BOWEL DISEASE
    ALAN DAVID LEVINE; Fiscal Year: 2010
    ..continuous remodeling of the ECM in IBD, a repair process quite distinct between UC and CD, engagement of select integrins on mucosal T cells modulates and potentially disrupts their signaling and function, thus contributing to ..
  40. Neutrophil Migration in Three Dimensions
    Jonathan S Reichner; Fiscal Year: 2013
    ..Adhesion Deficiency have normal numbers of neutrophils but they are genetically deficient in expression of integrins. Neutrophils in patients with Chronic Granulomatous Disease fail to produce adequate levels of microbiocidal ..
  41. Signaling Connections Controlling Cell Motility and Invasion
    David D Schlaepfer; Fiscal Year: 2013
    ..the importance of Rgnef in RhoA regulation, focal adhesion formation, and cell migration downstream of integrins. Here we extend these findings by Rgnef-/- reconstitution studies and show that Rgnef phosphoinositide lipid ..
  42. The Role of Galectins in Corneal Hem- and Lymphangiogenesis
    Noorjahan Panjwani; Fiscal Year: 2013
    ..HA and LA are predominantly mediated by a family of vascular endothelial cell growth factor (VEGF) receptors and integrins. In a recent study, we demonstrated that a carbohydrate- binding protein, galectin-3 (Gal3) is a mediator of the ..
  43. c-Abl-mediated Suppression of Breast Cancer Development and Metastasis
    WILLIAM SCHIEMANN; Fiscal Year: 2013
    ..We will manipulate, both positively and negatively, the expression of [unreadable]1 and [unreadable]3 integrins and their effectors to gauge their function in driving c-Abl inactivation during specific stages of TNBC ..
  44. Mechanical Signaling Mechanisms in Cardiac Tissue
    David E Dostal; Fiscal Year: 2013
    ..In Aim 1, we characterize the mechanisms by which 21 integrin and other 2 integrins couple mechanical stretch to activation of JNK, p38 and Akt and determine the role of these interactions on ..
  45. STUDIES ON THE STRUCTURE OF BASEMENT MEMBRANES
    BILLY GERALD HUDSON; Fiscal Year: 2013
    ..for usherin, a defective protein in Usher syndrome, for bacterial Dr adhesins in chronic pyelonephritis, and for integrins. We hypothesize that the quaternary structure of the 7S dodecamer is stabilized by both non-disulfide (..
  46. INTEGRIN SIGNALING IN HEMOSTASIS AND BLOOD DISEASES
    Sanford J Shattil; Fiscal Year: 2012
    Cell-extracellular matrix interactions are tightly regulated by "inside-out" signals that activate integrins. Integrin ligation and clustering localize and activate proteins at cell adhesion sites to initiate "outside-in" signals that ..
  47. Polarization and directed cell movements in engineered cellular environments
    Deborah E Leckband; Fiscal Year: 2010
    ..validation of these approaches will lay the foundation for future investigations of additional factors such as integrins, growth factors, substrate stiffness, or any number of parameters relevant to human development and disease...
  48. Identification of Mechanically Sensitive Proteins in Early Development
    Douglas W DeSimone; Fiscal Year: 2013
    ..cells sense local stresses, which typically are transduced through adhesive specializations involving cadherins, integrins and the cytoskeleton...
  49. Spatiotemporal Regulation of Membrane Raft Trafficking in Virus Activated Cells
    Tione Buranda; Fiscal Year: 2012
    ..GPI)-anchored protein decay accelerating factor (DAF/CD55) and low affinity state ???3 integrins in a manner that parallels the results obtained from infectivity assays using live virions...
  50. Very Late Antigen Integrin Activity on T Cells
    Yoji Shimizu; Fiscal Year: 2010
    ..In the immune system, the functional activity of integrins expressed on T lymphocytes is dynamically regulated by the activation state of the T cell in order to promote ..
  51. Metastatic protein network in BRAFV600E positive human thyroid cancers
    Carmelo Nucera; Fiscal Year: 2013
    ..g. thrombospondin-1 (TSP-1)) and receptors (integrins), including the integrin-linked kinases (i.e...
  52. Novel Molecules in Calcium Signaling in Platelets
    Wolfgang Bergmeier; Fiscal Year: 2013
    ..in platelets, is a central component of Ca2+-dependent activation of Rap1 and [unreadable]1/[unreadable]3 integrins. Integrin activation in the absence of CD-GEFI required signaling by protein kinase C (PKC) and the Gai-coupled ..
  53. TARGETING ONCOGENE EXPRESSION TO SKIN IN TRANSGENIC MICE
    DENNIS ROOP; Fiscal Year: 2013
    ..and effectors of mutant p53 converge on cell cycle regulation and signaling from extracelluar matrix components, integrins and Rho effectors, that we believe promote aggressively growing and invasive tumors...
  54. Small Molecule Inhibitors for the Oncogenic Protein Tyrosine Phosphatase SHP2
    Zhong Yin Zhang; Fiscal Year: 2013
    ..SHP2 is required for Ras/ERK1/2 activation downstream of most receptor tyrosine kinases, cytokine receptors, and integrins. In addition, gain-of-function SHP2 mutations are known to cause the autosomal dominant disorder Noonan Syndrome,..
  55. MHC class II-Associated Endothelial Dysfunction
    Joseph Holoshitz; Fiscal Year: 2010
    ..1) Is CRT the SE-binding receptor in EC?;1.2) Is CD91 acting as a co-receptor in EC?;1.3) What is the role of 2 integrins in SE signaling in EC?;1...
  56. Regulation of neutrophil migration by Activated Protein C
    Minsoo Kim; Fiscal Year: 2010
    ..Interaction of cell surface integrins with their counterpart ligands, which are expressed on the endothelial surface, results in the localization and ..
  57. MMPs, Integrins and Microglial activation in HAND
    KATHLEEN ANNE MAGUIRE-ZEISS; Fiscal Year: 2013
    ..Of interest, however, is the potential for MMPs to generate ligands for integrins that are highly expressed on microglia...
  58. Macrophage Infiltration of Renal Tissue via beta-3 Integrins and Agrin
    Scott D Blystone; Fiscal Year: 2013
    ..renal basement membrane is mediated by an interaction between the proteoglycan agrin and phosphorylated 23 integrins. In this application we will assess the role of 23 integrins and their phosphorylation in migration to renal ..
  59. Histone deacetylases and atherosclerosis
    Nilamadhab Mishra; Fiscal Year: 2010
    ..We will also measure cytokine, chemokines, integrins and adhesion molecules in macrophages expressing different amount of HDAC9 upon IPS stimulation...
  60. Mechanisms of glomerular disesase progression
    Jeffrey R Schelling; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Integrins are extracellular matrix receptors, which regulate vital cell functions. The [unreadable]8 subunit partners with alpha-v, and expression is restricted to kidney, brain, and placenta...
  61. Mechanically Stressed VSMC: A Role for Slingshot Phosphatase in Inflammation
    Alejandra San Martin; Fiscal Year: 2013
    ..We hypothesize that in response to mechanical stress, integrins activate the Nox4-based NADPH oxidase to produce H2O2 that induces SSH1IL-mediated cofilin activation within the ..
  62. A Novel Brachytherapy Agent for GBM
    FRANK CALZONE; Fiscal Year: 2013
    ..b>Integrins are heterodimeric receptors found on the surface of GBM cells and angiogenic vasculature;they facilitate ..
  63. ROLE OF MONONUCLEAR LEUKOCYTES IN IMMUNITY
    Samuel Silverstein; Fiscal Year: 2009
    ..Moreover, we discovered that PMN genetically deficient in a2-integrins phagocytose and kill S.epidermidis as efficiently as wild-type PMN in fibrin gels...
  64. Suppression of glioma invasion by a bicistronic constuct
    JASTI RAO; Fiscal Year: 2007
    ..3) Assess the effect of the bicistronic Ad-uPAR-pl6 construct on the expression of integrins (particularly avlI3) and molecules involved in signaling pathways mediated by integrins...
  65. Regulation of integrin function by divalent cations
    Edward Plow; Fiscal Year: 2004
    ..Binding of fibrinogen to these two beta3 integrins, as well as most ligands to most integrins (there are more than 20 integrins), is divalent ion dependent, and ..
  66. Cell Entry of Human Metapneumovirus
    John Williams; Fiscal Year: 2009
    ..Several pathogenic human viruses utilize RGD-binding integrins as receptors or co-receptors, including adenovirus, Coxsackievirus, parechovirus, rotavirus and human herpes ..
  67. HANTAVIRUS CELL INTERACTIONS
    ERICH MACKOW; Fiscal Year: 2003
    ..We have recently determined that alphanubeta3 and alphaIIbbeta3 integrins are cellular receptors for pathogenic, but not non-pathogenic, hantaviruses and this finding directly relates ..
  68. Regulation of Vascular Tone and Ca channels by Integrins
    Michael Davis; Fiscal Year: 2009
    DESCRIPTION (provided by applicant): Interactions between vascular integrins and extracellular matrix (ECM) components of the blood vessel wall are important determinants of arteriolar tone and blood flow control...
  69. Modeling PCa Bone Metastasis: Dual Role of E-selectin Ligands and Integrins
    STEVEN RUSSELL BARTHEL; Fiscal Year: 2012
    ..are upregulated and functional on bone-metastatic PCa cells, while other groups have shown that b1 and b3 integrins correspond to PCa cell avidity for bone marrow endothelial cells (BMEC) and to metastatic potential...
  70. Functional Roles of Integrins in Modulating Neural Responses of Mechanically Sens
    Michael Hadjiargyrou; Fiscal Year: 2007
    ..The current proposal seeks to investigate the functional roles that trans-membrane proteins, integrins, play in modulating neural responses of cutaneous mechanoreceptors...
  71. INTEGRIN REGULATION AND FUNCTIONS IN ADULT BRAIN
    Christine Gall; Fiscal Year: 2007
    ..Research in this program has shown that integrins are concentrated at synapses and influence neurotrophin expression, and glutamate receptor and ion channel ..
  72. Beta2 Integrin Activation and Signaling
    Vineet Gupta; Fiscal Year: 2010
    The leukocyte specific beta2 integrins are central to the biological function of these cells...