M J Humphries

Summary

Affiliation: University of Manchester
Country: UK

Publications

  1. ncbi Integrin structure: heady advances in ligand binding, but activation still makes the knees wobble
    Martin J Humphries
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, 2 205 Stopford Building, Oxford Road, Manchester, UK M13 9PT
    Trends Biochem Sci 28:313-20. 2003
  2. ncbi Integrin structure
    M J Humphries
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Road, Manchester M13 9PT, U K
    Biochem Soc Trans 28:311-39. 2000
  3. ncbi Integrin activation: the link between ligand binding and signal transduction
    M J Humphries
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Road, Manchester M13 9PT, UK
    Curr Opin Cell Biol 8:632-40. 1996
  4. ncbi Integrin cell adhesion receptors and the concept of agonism
    M J Humphries
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Road, Manchester, UK M13 9PT
    Trends Pharmacol Sci 21:29-32. 2000
  5. ncbi The structure of cell-adhesion molecules
    M J Humphries
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, UK
    Trends Cell Biol 8:78-83. 1998
  6. ncbi Cell adhesion assays
    M J Humphries
    School of Biological Sciences Wellcome Trust Centre for Cell Matrix Research, University of Manchester, 2 205 Stopford Building, Oxford Road, Manchester M13 9PT
    Mol Biotechnol 18:57-61. 2001
  7. ncbi Insights into integrin-ligand binding and activation from the first crystal structure
    Martin J Humphries
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, UK
    Arthritis Res 4:S69-78. 2002
  8. ncbi Mechanisms of integration of cells and extracellular matrices by integrins
    M J Humphries
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Road, Manchester M13 9PT, UK
    Biochem Soc Trans 32:822-5. 2004
  9. ncbi Monoclonal antibodies as probes of integrin priming and activation
    M J Humphries
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Road, Manchester M13 9PT, UK
    Biochem Soc Trans 32:407-11. 2004
  10. ncbi Mapping functional residues onto integrin crystal structures
    Martin J Humphries
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Road, United Kingdom
    Curr Opin Struct Biol 13:236-43. 2003

Collaborators

Detail Information

Publications86

  1. ncbi Integrin structure: heady advances in ligand binding, but activation still makes the knees wobble
    Martin J Humphries
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, 2 205 Stopford Building, Oxford Road, Manchester, UK M13 9PT
    Trends Biochem Sci 28:313-20. 2003
    ..Like all major advances, however, these studies have raised more questions than they have answered about issues such as the mechanisms underlying ligand-binding specificity and long-range conformational regulation...
  2. ncbi Integrin structure
    M J Humphries
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Road, Manchester M13 9PT, U K
    Biochem Soc Trans 28:311-39. 2000
    ..Our current understanding of the molecular basis of integrin function is therefore compiled from the results of a large number of studies that have employed a wide range of complementary technologies...
  3. ncbi Integrin activation: the link between ligand binding and signal transduction
    M J Humphries
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Road, Manchester M13 9PT, UK
    Curr Opin Cell Biol 8:632-40. 1996
    ..These insights now permit a better visualization of the intricate molecular switch that controls the adhesive phenotype...
  4. ncbi Integrin cell adhesion receptors and the concept of agonism
    M J Humphries
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Road, Manchester, UK M13 9PT
    Trends Pharmacol Sci 21:29-32. 2000
    ..Sufficient evidence is now available to pose the question of whether integrins should be classified as true signalling receptors; this article both reviews this evidence and attempts to identify remaining gaps...
  5. ncbi The structure of cell-adhesion molecules
    M J Humphries
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, UK
    Trends Cell Biol 8:78-83. 1998
    ..This review discusses how these studies have helped explain the unique functional roles of the different families of adhesion molecules...
  6. ncbi Cell adhesion assays
    M J Humphries
    School of Biological Sciences Wellcome Trust Centre for Cell Matrix Research, University of Manchester, 2 205 Stopford Building, Oxford Road, Manchester M13 9PT
    Mol Biotechnol 18:57-61. 2001
    ..First, an attachment assay, which employs a colorimetric detection of bound cells, and second, a spreading assay, which employs phase contrast microscopy to measure the flattening of adherent cells...
  7. ncbi Insights into integrin-ligand binding and activation from the first crystal structure
    Martin J Humphries
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, UK
    Arthritis Res 4:S69-78. 2002
    ....
  8. ncbi Mechanisms of integration of cells and extracellular matrices by integrins
    M J Humphries
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Road, Manchester M13 9PT, UK
    Biochem Soc Trans 32:822-5. 2004
    ..Two main topics are covered: the adaptation of integrin structure for bi-directional signalling and the integration of integrin signalling with other receptors...
  9. ncbi Monoclonal antibodies as probes of integrin priming and activation
    M J Humphries
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Road, Manchester M13 9PT, UK
    Biochem Soc Trans 32:407-11. 2004
    ..Although both clustering and conformation are important for integrin function, the latter will be the main focus of this article; in particular, the importance of monoclonal antibodies for the study of integrin shape changes...
  10. ncbi Mapping functional residues onto integrin crystal structures
    Martin J Humphries
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Road, United Kingdom
    Curr Opin Struct Biol 13:236-43. 2003
    ..In the past two years, this combining of structure and function has led to the development of novel hypotheses for the mechanisms of integrin regulation...
  11. ncbi Integrin alpha 4 beta 1-mediated melanoma cell adhesion and migration on vascular cell adhesion molecule-1 (VCAM-1) and the alternatively spliced IIICS region of fibronectin
    A P Mould
    School of Biological Sciences, University of Manchester, United Kingdom
    J Biol Chem 269:27224-30. 1994
    ..The results revealed a hierarchy of ligand affinities that mirrored their adhesive activity (rsVCAM-1 > fibronectin variants containing CS1 >> other fibronectin variants)...
  12. ncbi Monoclonal antibodies identify residues 199-216 of the integrin alpha2 vWFA domain as a functionally important region within alpha2beta1
    D S Tuckwell
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK
    Biochem J 350:485-93. 2000
    ..e. they are intimately associated with the collagen-binding site, responsive to conformational changes at the collagen-binding site and sensitive to events initiated outside the vWFA domain...
  13. ncbi Identification of amino acid residues that form part of the ligand-binding pocket of integrin alpha5 beta1
    A P Mould
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
    J Biol Chem 273:25664-72. 1998
    ..Furthermore, as Ser156-Trp157 is unique to the alpha5 subunit, it may be responsible for the specific recognition of RRETAWA by alpha5 beta1...
  14. ncbi The A-domain of integrin alpha 2 binds specifically to a range of collagens but is not a general receptor for the collagenous motif
    D S Tuckwell
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, UK
    Eur J Biochem 241:732-9. 1996
    ..By inference, these findings indicate the existence of an integrin-specific sequence motif within collagenous ligands recognised by the alpha 2 A-domain...
  15. ncbi Regulation of integrin function: evidence that bivalent-cation-induced conformational changes lead to the unmasking of ligand-binding sites within integrin alpha5 beta1
    A P Mould
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, Manchester, M13 9PT, UK
    Biochem J 331:821-8. 1998
    ....
  16. ncbi Evidence that monoclonal antibodies directed against the integrin beta subunit plexin/semaphorin/integrin domain stimulate function by inducing receptor extension
    A Paul Mould
    Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
    J Biol Chem 280:4238-46. 2005
    ..Second, the PSI domain is important for the transduction of conformational changes from the knee to head. Third, unbending is likely to provide a general mechanism for control of integrin-ligand recognition...
  17. ncbi Dual functionality of the anti-beta1 integrin antibody, 12G10, exemplifies agonistic signalling from the ligand binding pocket of integrin adhesion receptors
    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 Biol Chem 280:10234-43. 2005
    ..We propose that either ligand-specific transmembrane conformational changes or ligand-specific differences in the kinetics of transmembrane domain separation underlie integrin agonism...
  18. ncbi Identification of a novel heparin-binding site in the alternatively spliced IIICS region of fibronectin: roles of integrins and proteoglycans in cell adhesion to fibronectin splice variants
    Z Mostafavi-Pour
    Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, 2.205 Stopford Building, Oxford Road, M13 9PT, Manchester, UK
    Matrix Biol 20:63-73. 2001
    ..Anti-integrin antibodies and exogenous heparin were capable of inhibiting melanoma cell adhesion to H/95 and in this case adhesion was due primarily to cell-surface proteoglycan and not integrin binding...
  19. ncbi Molecular basis of ligand recognition by integrin alpha 5beta 1. I. Specificity of ligand binding is determined by amino acid sequences in the second and third NH2-terminal repeats of the alpha subunit
    A P Mould
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
    J Biol Chem 275:20324-36. 2000
    ....
  20. ncbi Defining the topology of integrin alpha5beta1-fibronectin interactions using inhibitory anti-alpha5 and anti-beta1 monoclonal antibodies. Evidence that the synergy sequence of fibronectin is recognized by the amino-terminal repeats of the alpha5 subunit
    A P Mould
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
    J Biol Chem 272:17283-92. 1997
    ..These findings provide new insights into the mechanisms, specificity, and topology of integrin-ligand interactions...
  21. ncbi Alpha4 integrin binding interfaces on VCAM-1 and MAdCAM-1. Integrin binding footprints identify accessory binding sites that play a role in integrin specificity
    P Newham
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Road, Manchester, M13 9PT, United Kingdom
    J Biol Chem 272:19429-40. 1997
    ..The analogous region in MAdCAM-1 is markedly different in size and sequence and when mutated abolishes integrin binding activity...
  22. ncbi Cell adhesion to fibrillin-1 molecules and microfibrils is mediated by alpha 5 beta 1 and alpha v beta 3 integrins
    Daniel V Bax
    United Kingdom Centre for Tissue Engineering, School of Biological Sciences, University of Manchester, United Kingdom
    J Biol Chem 278:34605-16. 2003
    ....
  23. ncbi Integrin alpha5beta1 and ADAM-17 interact in vitro and co-localize in migrating HeLa cells
    Daniel V Bax
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, The Michael Smith Building, Oxford Road, Manchester M13 9PT
    J Biol Chem 279:22377-86. 2004
    ..We postulate that the interaction of ADAM-17 with alpha(5)beta(1) may target or modulate its metalloproteolytic activity...
  24. ncbi A structure prediction for the ligand-binding region of the integrin beta subunit: evidence for the presence of a von Willebrand factor A domain
    D S Tuckwell
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, UK
    FEBS Lett 400:297-303. 1997
    ..Primary, secondary and tertiary structure analyses indicate that the region folds into a von Willebrand factor A-domain, thereby potentially placing a previously characterised module at the centre of a key functional region...
  25. ncbi Novel activating and inactivating mutations in the integrin beta1 subunit A domain
    Stephanie J Barton
    The Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, Manchester M13 9PT, UK
    Biochem J 380:401-7. 2004
    ..Although these changes are grossly similar to those defined in the A domains found in some integrin alpha subunits, movement of the alpha1 helix appears to play a more prominent role in betaA domain activation...
  26. ncbi The alternatively spliced type III connecting segment of fibronectin is a zinc-binding module
    Janet A Askari
    Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom
    Matrix Biol 26:485-93. 2007
    ..Taken together, these data demonstrate that the IIICS region of FN is a novel zinc-binding module...
  27. ncbi Mechanisms of VCAM-1 and fibronectin binding to integrin alpha 4 beta 1: implications for integrin function and rational drug design
    M J Humphries
    School of Biological Sciences, University of Manchester, UK
    Ciba Found Symp 189:177-91; discussion 191-9. 1995
    ..Since IDSP-like sequences are probably used by other integrin-binding immunoglobulins, derivatives of these peptides may turn out to be the forerunners of a new generation of therapeutic agents with multiple applications...
  28. ncbi Regulation of the extracellular ligand binding activity of integrins
    C Fernandez
    School of Biological Sciences, University of Manchester, Room 2 205 Stopford Building, Oxford Road, Manchester M13 9PT, United Kingdom man ac uk
    Front Biosci 3:d684-700. 1998
    ..In addition, the mechanisms by which the ligand binding event is regulated through conformational change will be addressed, and the potential role of intracellular cytoplasmic proteins will be discussed...
  29. ncbi Conformation dependence of integrin-type II collagen binding. Inability of collagen peptides to support alpha 2 beta 1 binding, and mediation of adhesion to denatured collagen by a novel alpha 5 beta 1-fibronectin bridge
    D S Tuckwell
    School of Biological Sciences, University of Manchester, UK
    J Cell Sci 107:993-1005. 1994
    ..In particular, these data suggest that, unlike other integrin ligands, a synthetic peptide-based approach is not suitable for the identification of collagen active sites...
  30. ncbi Protein secondary structure prediction by the analysis of variation and conservation in multiple alignments
    D S Tuckwell
    School of Biological Sciences, University of Manchester, UK
    Comput Appl Biosci 11:627-32. 1995
    ..The algorithm presented here, plus the assessment of the accuracy of prediction generated by this method, should enable this predictive approach to receive informed general use...
  31. ncbi The integrin alpha1 A-domain is a ligand binding site for collagens and laminin
    D A Calderwood
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, Manchester, M13 9PT, United Kingdom
    J Biol Chem 272:12311-7. 1997
    ..The values obtained were similar to those reported for intact integrin binding, suggesting that the A-domain is the major collagen binding site in the alpha1beta1 and alpha2beta1 integrins...
  32. ncbi Calpha-H...O = C hydrogen bonds contribute to the specificity of RGD cell-adhesion interactions
    Jordi Bella
    Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester
    BMC Struct Biol 5:4. 2005
    ..The central Gly residue also appears to be in close contact with the integrin surface in these structures...
  33. ncbi 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
    Dimitra Valdramidou
    Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
    J Biol Chem 283:32704-14. 2008
    ....
  34. ncbi Interaction of filamin A with the integrin beta 7 cytoplasmic domain: role of alternative splicing and phosphorylation
    Mark A Travis
    School of Biological Sciences, 2 205 Stopford Building, Wellcome Trust Centre for Cell Matrix Research, University of Manchester, The Michael Smith Building, Oxford Road, Manchester M13 9PT, UK
    FEBS Lett 569:185-90. 2004
    ..In addition, we provide evidence that phosphorylation of the splice variant region is unlikely to represent the mechanism by which binding is reduced...
  35. ncbi Integrin adhesion receptors: structure, function and implications for biomedicine
    P Newham
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, UK
    Mol Med Today 2:304-13. 1996
    ..Recent years have seen major advances in our understanding of integrin-ligand interactions, and have revealed a structurally dynamic family of receptors capable of translating information into and out of the cell...
  36. ncbi Cell adhesion to fibrillin-1: identification of an Arg-Gly-Asp-dependent synergy region and a heparin-binding site that regulates focal adhesion formation
    Daniel V Bax
    UK Centre for Tissue Engineering, University of Manchester, Manchester, M13 9PT, UK
    J Cell Sci 120:1383-92. 2007
    ..These integrin and syndecan adhesion motifs juxtaposed on fibrillin-1 are evolutionarily conserved and reminiscent of similar functional elements on fibronectin, highlighting their crucial functional importance...
  37. ncbi Activation of integrin alpha5beta1 delays apoptosis of Ntera2 neuronal cells
    Rosemary M Gibson
    Faculty of Life Sciences, University of Manchester, 1 124 Stopford Building, Oxford Road, Manchester, M13 9PT, UK
    Mol Cell Neurosci 28:588-98. 2005
    ..The antibody 12G10 specifically delayed loss of phosphorylation of AKT on serine 473, and GSK-3beta on serine 9, induced by serum withdrawal, suggesting that these kinases are critical sensors of integrin activation on neuronal cells...
  38. ncbi Mapping the ligand-binding pocket of integrin alpha5beta1 using a gain-of-function approach
    A Paul Mould
    Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, Michael Smith Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK
    Biochem J 424:179-89. 2009
    ..These results will aid the development of reagents that block integrin alpha5beta1 functions in vivo...
  39. ncbi DrhoGEF3 encodes a new Drosophila DH domain protein that exhibits a highly dynamic embryonic expression pattern
    M S Hicks
    Wellcome Trust Center for Cell Matrix Research, School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Road, Manchester, M13 9PT, UK
    Dev Genes Evol 211:263-7. 2001
    ..DrhoGEF3 is subsequently expressed in the visceral mesoderm, at the sites of muscle attachment and in specific groups of sub-epidermal cells. The possible function of such a dynamically expressed signalling molecule is discussed...
  40. ncbi An integrin-alpha4-14-3-3zeta-paxillin ternary complex mediates localised Cdc42 activity and accelerates cell migration
    Nicholas O Deakin
    Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK
    J Cell Sci 122:1654-64. 2009
    ..Taken together, these data identify a key signalling nexus mediating alpha4 integrin-dependent migration...
  41. ncbi Regulation of integrin function through conformational complexity: not simply a knee-jerk reaction?
    A Paul Mould
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK
    Curr Opin Cell Biol 16:544-51. 2004
    ..This conformational complexity is likely to permit fine-tuning of integrin function through regulation of ligand-binding affinity and intracellular signalling...
  42. ncbi CD14 is a ligand for the integrin alpha4beta1
    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, United Kingdom
    FEBS Lett 581:757-63. 2007
    ..In summary, CD14 is a novel ligand for alpha4beta1, exhibiting similar activation-state dependent binding characteristics as other alpha4beta1 ligands. The biological relevance of this interaction will be the subject of further studies...
  43. ncbi Linking integrin conformation to function
    Janet A Askari
    Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK
    J Cell Sci 122:165-70. 2009
    ..In this Commentary, we pose some of the key remaining questions that surround integrin structure-function relationships and review the evidence that supports the current models...
  44. ncbi Focal adhesions are sites of integrin extension
    Janet A Askari
    Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK
    J Cell Biol 188:891-903. 2010
    ..These results demonstrate definitely that major quaternary rearrangements of beta1-integrin subunits occur in adherent cells and that conversion from a bent to extended form takes place at focal adhesions...
  45. ncbi Role of ADMIDAS cation-binding site in ligand recognition by integrin alpha 5 beta 1
    A Paul Mould
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
    J Biol Chem 278:51622-9. 2003
    ....
  46. ncbi E-cadherin is a ligand for integrin alpha2beta1
    John D Whittard
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Road, Manchester M13 9PT, UK
    Matrix Biol 21:525-32. 2002
    ..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...
  47. ncbi Conformational changes in the integrin beta A domain provide a mechanism for signal transduction via hybrid domain movement
    A Paul Mould
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
    J Biol Chem 278:17028-35. 2003
    ..Taken together, these data suggest that the transduction of conformational changes through betaA involves shape shifting in the alpha7 helix region, which is linked to a swing of the hybrid domain away from the alpha subunit...
  48. ncbi Integrin activation involves a conformational change in the alpha 1 helix of the beta subunit A-domain
    A Paul Mould
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
    J Biol Chem 277:19800-5. 2002
    ..The mechanism of beta subunit A-domain activation appears to be distinct from that of the A-domains found in some integrin alpha subunits...
  49. ncbi Structure of an integrin-ligand complex deduced from solution x-ray scattering and site-directed mutagenesis
    A Paul Mould
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
    J Biol Chem 278:39993-9. 2003
    ..Our data provide the first view of a complex between an integrin and a macromolecular ligand in solution, at a nominal resolution of approximately 10 A...
  50. ncbi Elucidation of the structural features of heparan sulfate important for interaction with the Hep-2 domain of fibronectin
    M Lyon
    Cancer Research Campaign Department of Medical Oncology, University of Manchester, Christie Hospital NHS Trust, Manchester M20 4BX, United Kingdom
    J Biol Chem 275:4599-606. 2000
    ..18, 1468-1479) in which two separate, positively charged clusters, involving up to 11 basic amino acid residues (mostly arginines with their preferential ability to co-ordinate sulfate groups), could form a single extended binding site...
  51. ncbi Generation of a minimal alpha5beta1 integrin-Fc fragment
    A P Coe
    Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road, Manchester, United Kingdom
    J Biol Chem 276:35854-66. 2001
    ..Each of these minimally truncated integrins displayed the antibody binding characteristics of alpha(5)beta(1) purified from human placenta and bound ligand with the same apparent affinity as the native receptor...
  52. ncbi Alpha2(VIII) collagen substrata enhance endothelial cell retention under acute shear stress flow via an alpha2beta1 integrin-dependent mechanism: an in vitro and in vivo study
    Neill J Turner
    UK Centre for Tissue Engineering, Manchester, United Kingdom
    Circulation 114:820-9. 2006
    ....
  53. ncbi 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...
  54. ncbi Integrin-syndecan cooperation governs the assembly of signalling complexes during cell spreading
    Martin J Humphries
    Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, UK
    Novartis Found Symp 269:178-88; discussion 188-92, 223-30. 2005
    ..These findings demonstrate that different integrins can signal to induce focal adhesion formation by different mechanisms...
  55. ncbi p190RhoGAP is the convergence point of adhesion signals from alpha 5 beta 1 integrin and syndecan-4
    Mark D Bass
    Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK
    J Cell Biol 181:1013-26. 2008
    ..This molecular mechanism explains the cooperation between extracellular matrix receptors during cell adhesion...
  56. ncbi A novel gain-of-function mutation of the integrin alpha2 VWFA domain
    Alexis Aquilina
    School of Biological Sciences, University of Manchester, Manchester, UK
    Eur J Biochem 269:1136-44. 2002
    ..These data indicate that residue E318 plays a novel and important role in modulating alpha2 VWFA domain--ligand binding and may be involved in the conformational changes associated with its regulation...
  57. ncbi Cell-substrate adhesion assays
    M J Humphries
    University of Manchester, Manchester, United Kingdom
    Curr Protoc Cell Biol . 2001
    ..Nonattached cells are removed, and the percent of added cells attached to the substrate is quantified by crystal violet staining...
  58. ncbi Preconditioning injury-induced neurite outgrowth of adult rat sensory neurons on fibronectin is mediated by mobilisation of axonal alpha5 integrin
    Natalie J Gardiner
    Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, UK
    Mol Cell Neurosci 35:249-60. 2007
    ..We show that alpha5 integrin localises to adhesion complexes in the growth cone and neurites of preconditioned neurons, but not control neurons...
  59. ncbi 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
  60. ncbi Integrin-specific signaling pathways controlling focal adhesion formation and cell migration
    Zohreh Mostafavi-Pour
    School of Biological Sciences, University of Manchester, Manchester M13 9PT, UK
    J Cell Biol 161:155-67. 2003
    ....
  61. ncbi Proteomic analysis of integrin-associated complexes identifies RCC2 as a dual regulator of Rac1 and Arf6
    Jonathan D Humphries
    Wellcome Trust Centre for Cell Matrix Research, University of Manchester, Manchester, UK
    Sci Signal 2:ra51. 2009
    ..This proteomics workflow now opens the way to further dissection and systems-level analyses of adhesion signaling...
  62. ncbi Giving off mixed signals--distinct functions of alpha5beta1 and alphavbeta3 integrins in regulating cell behaviour
    Mark R Morgan
    Faculty of Life Sciences, Wellcome Trust Centre for Cell Matrix Research, University of Manchester, Manchester, UK
    IUBMB Life 61:731-8. 2009
    ..By considering the GTPase and kinase signalling and trafficking of two such closely-related receptors, we begin to understand how cell migration is coordinated...
  63. ncbi Syndecan-4-dependent Rac1 regulation determines directional migration in response to the extracellular matrix
    Mark D Bass
    Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, England, UK
    J Cell Biol 177:527-38. 2007
    ....
  64. ncbi Therapeutic ultrasound bypasses canonical syndecan-4 signaling to activate rac1
    Claire M Mahoney
    Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, United Kingdom and Smith and Nephew, York Science Park, Heslington, York YO10 5DF, United Kingdom
    J Biol Chem 284:8898-909. 2009
    ..By substituting for one of the key axes of adhesion-dependent signaling, ultrasound therapy has considerable potential as a clinical technique...
  65. ncbi An unraveling tale of how integrins are activated from within
    Mark A Travis
    Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road, Manchester M13 9PT, UK
    Trends Pharmacol Sci 24:192-7. 2003
    ....
  66. ncbi Integrin-binding RGD peptides induce rapid intracellular calcium increases and MAPK signaling in cortical neurons
    P Marc D Watson
    Faculty of Life Sciences, Michael Smith Building, University of Manchester, Manchester, M13 9PT, UK
    Mol Cell Neurosci 34:147-54. 2007
    ....
  67. ncbi 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
    ..Here we survey the evidence that synergistic signalling is involved in controlling adhesive function and the regulation of cell behaviour in response to the external environment...
  68. ncbi Identification of multiple integrin beta1 homologs in zebrafish (Danio rerio)
    A Paul Mould
    Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, Michael Smith Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK
    BMC Cell Biol 7:24. 2006
    ....
  69. ncbi Cytoplasmic interactions of syndecan-4 orchestrate adhesion receptor and growth factor receptor signalling
    Mark D Bass
    Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, Manchester M13 9PT, U K
    Biochem J 368:1-15. 2002
    ..These conclusions also offer an insight into the role of syndecan-4 in vivo, and are consistent with phenotypes generated as a consequence of abnormal syndecan-4 expression in pathologies and gene disruption studies...
  70. ncbi Cell adhesion assays
    Martin J Humphries
    University of Manchester, Oxford Road, Manchester, M13 9PT, UK
    Methods Mol Biol 522:203-10. 2009
    ....
  71. ncbi Syndecans shed their reputation as inert molecules
    Mark D Bass
    Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK
    Sci Signal 2:pe18. 2009
    ..In this Perspective, we summarize the current understanding of receptor interplay and identify the challenges that face investigators of adhesion- and growth factor-dependent signaling...
  72. ncbi The "linker" region (amino acids 38-47) of the disintegrin elegantin is a novel inhibitory domain of integrin alpha5beta1-dependent cell adhesion on fibronectin: evidence for the negative regulation of fibronectin synergy site biological activit
    Rushika Sumathipala
    Laboratory of Thrombosis and Vascular Remodelling, Division of Cardiovascular Medicine, King's College London School of Medicine, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, United Kingdom
    J Biol Chem 281:37686-96. 2006
    ..These data demonstrate a novel biological function for a disintegrin domain that antagonizes integrin-mediated cell adhesion...
  73. ncbi Cell biology: adhesion articulated
    A Paul Mould
    Nature 432:27-8. 2004
  74. ncbi A specific alpha5beta1-integrin conformation promotes directional integrin translocation and fibronectin matrix formation
    Katherine Clark
    Craniofacial Developmental Biology and Regeneration Branch, NIDCR, NIH, Bethesda, MA 20892, USA
    J Cell Sci 118:291-300. 2005
    ....
  75. ncbi Fibronectin regulates latent transforming growth factor-beta (TGF beta) by controlling matrix assembly of latent TGF beta-binding protein-1
    Sarah L Dallas
    Department of Oral Biology, School of Dentistry, University of Missouri, Kansas City, Missouri 64108, USA
    J Biol Chem 280:18871-80. 2005
    ..These studies highlight a nonredundant role for fibronectin in LTBP1 assembly into the ECM and suggest a novel role for fibronectin in regulation of TGF beta via LTBP1 interactions...
  76. ncbi Regulation of alpha5beta1 integrin conformation and function by urokinase receptor binding
    Ying Wei
    Department of Medicine and Pulmonary and Critical Care Division, University of California, San Francisco, San Francisco, CA 94143, USA
    J Cell Biol 168:501-11. 2005
    ..Direct binding and regulation of alpha5beta1 by uPAR implies a modified "bent" integrin conformation can function in an alternative activation state with this and possibly other cis-acting membrane ligands...
  77. ncbi Site-directed perturbation of protein kinase C- integrin interaction blocks carcinoma cell chemotaxis
    Maddy Parsons
    Richard Dimbleby Cancer Research UK Department of Cancer Research, GKT School of Medicine, St Thomas Hospital, London SE1 7EH, United Kingdom
    Mol Cell Biol 22:5897-911. 2002
    ..Importantly, our findings outline a new concept as to how carcinoma cell chemotaxis is enhanced and provide a conceptual basis for interfering with tumor cell dissemination...
  78. ncbi Heparin-II domain of fibronectin is a vascular endothelial growth factor-binding domain: enhancement of VEGF biological activity by a singular growth factor/matrix protein synergism
    Errol S Wijelath
    Department of Surgery, Division of Vascular Surgery, Veterans Affairs Puget Sound Health Care System and the University of Washington School of Medicine, Seattle, USA
    Circ Res 99:853-60. 2006
    ..These data also highlight a new function for the Fn C-terminal heparin-binding domain that may have important implications for angiogenesis and tumor growth...
  79. ncbi Molecular basis for the dynamic strength of the integrin alpha4beta1/VCAM-1 interaction
    Xiaohui Zhang
    Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, Florida 33136, USA
    Biophys J 87:3470-8. 2004
    ..Together, these findings provide a molecular explanation for the functionally relevant kinetic properties of the alpha4beta1/VCAM-1 interaction...
  80. ncbi Alternative splicing of the IIICS domain in fibronectin governs the role of the heparin II domain in fibrillogenesis and cell spreading
    Amy J Santas
    Department of Pathology, University of Wisconsin, Madison, Wisconsin 53706, USA
    J Biol Chem 277:13650-8. 2002
    ..We propose that alternative splicing of the IIICS domain modulates interactions between heparan sulfate proteoglycans and the Hep II domain and that this serves as a mechanism to control the biological activities of fibronectin...
  81. ncbi The integrins of the urochordate Ciona intestinalis provide novel insights into the molecular evolution of the vertebrate integrin family
    Richard Ewan
    Plant Molecular Science Group, University of Glasgow, Bower Building, G12 8QQ, UK
    BMC Evol Biol 5:31. 2005
    ..The publication of the genome of a basal chordate, Ciona intestinalis, provides a unique opportunity to gain further insight into how and when the expanded integrin supergene family found in vertebrates evolved...
  82. ncbi Rab25 associates with alpha5beta1 integrin to promote invasive migration in 3D microenvironments
    Patrick T Caswell
    Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK
    Dev Cell 13:496-510. 2007
    ..These data indicate that Rab25 contributes to tumor progression by directing the localization of integrin-recycling vesicles and thereby enhancing the ability of tumor cells to invade the extracellular matrix...
  83. ncbi Fibronectin-tissue transglutaminase matrix rescues RGD-impaired cell adhesion through syndecan-4 and beta1 integrin co-signaling
    Dilek Telci
    School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, United Kingdom
    J Biol Chem 283:20937-47. 2008
    ....
  84. ncbi Quantification of integrin receptor agonism by fluorescence lifetime imaging
    Maddy Parsons
    Randall Division of Cell and Molecular Biophysics, King s College London, New Hunt s House, Guys Campus, London, SE1 1UL, UK
    J Cell Sci 121:265-71. 2008
    ..This study provides insight into the dependence of the activity of small molecule anti-integrin compounds upon receptor conformation, and provides a novel quantitative assay for the validation of potential integrin antagonists...
  85. ncbi Evidence for the presence of a low-mass beta1 integrin on the cell surface
    Xiaobo Meng
    Manitoba Centre for Proteomics and Systems Biology, Department of Internal Medicine, University of Manitoba, 715 McDermot Avenue, Winnipeg, MB, Canada R3E 3P4
    J Cell Sci 118:4009-16. 2005
    ..The data also suggest that differences in glycosylation may be involved in defining the association between the integrin alpha and beta chains and the functional properties of these integrins...