T A Springer

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi request reprint An extracellular beta-propeller module predicted in lipoprotein and scavenger receptors, tyrosine kinases, epidermal growth factor precursor, and extracellular matrix components
    T A Springer
    Department of Pathology, Center for Blood Research and Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    J Mol Biol 283:837-62. 1998
  2. pmc Defining extracellular integrin alpha-chain sites that affect cell adhesion and adhesion strengthening without altering soluble ligand binding
    C Pujades
    Division of Tumor Virology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Biol Cell 8:2647-57. 1997
  3. ncbi request reprint Epitope mapping of antibodies to the C-terminal region of the integrin beta 2 subunit reveals regions that become exposed upon receptor activation
    C Lu
    Center for Blood Research, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 166:5629-37. 2001
  4. ncbi request reprint Ultrastructure and function of dimeric, soluble intercellular adhesion molecule-1 (ICAM-1)
    C D Jun
    Center for Blood Research and the Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 276:29019-27. 2001
  5. pmc A dimeric crystal structure for the N-terminal two domains of intercellular adhesion molecule-1
    J M Casasnovas
    The Center for Blood Research and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 95:4134-9. 1998
  6. pmc Reversibly locking a protein fold in an active conformation with a disulfide bond: integrin alphaL I domains with high affinity and antagonist activity in vivo
    M Shimaoka
    The Center for Blood Research and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 98:6009-14. 2001
  7. pmc Lymphocyte adhesion through very late antigen 4: evidence for a novel binding site in the alternatively spliced domain of vascular cell adhesion molecule 1 and an additional alpha 4 integrin counter-receptor on stimulated endothelium
    R H Vonderheide
    Department of Pathology, Harvard Medical School, Boston, Massachusetts
    J Exp Med 175:1433-42. 1992
  8. ncbi request reprint Amino acid residues in the PSI domain and cysteine-rich repeats of the integrin beta2 subunit that restrain activation of the integrin alpha(X)beta(2)
    Q Zang
    Center for Blood Research, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 276:6922-9. 2001
  9. ncbi request reprint Kinetic and mechanical basis of rolling through an integrin and novel Ca2+-dependent rolling and Mg2+-dependent firm adhesion modalities for the alpha 4 beta 7-MAdCAM-1 interaction
    M de Château
    The Center for Blood Research, Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
    Biochemistry 40:13972-9. 2001
  10. pmc Lymphocyte function-associated antigen-1 binding residues in intercellular adhesion molecule-2 (ICAM-2) and the integrin binding surface in the ICAM subfamily
    J M Casasnovas
    The Center for Blood Research and Harvard Medical School, Department of Pathology, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 96:3017-22. 1999

Collaborators

Detail Information

Publications109 found, 100 shown here

  1. ncbi request reprint An extracellular beta-propeller module predicted in lipoprotein and scavenger receptors, tyrosine kinases, epidermal growth factor precursor, and extracellular matrix components
    T A Springer
    Department of Pathology, Center for Blood Research and Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    J Mol Biol 283:837-62. 1998
    ..YWTD beta-propellers have a circular folding pattern that brings neighboring modules into close proximity, and may have important consequences for the architecture of multi-domain proteins...
  2. pmc Defining extracellular integrin alpha-chain sites that affect cell adhesion and adhesion strengthening without altering soluble ligand binding
    C Pujades
    Division of Tumor Virology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Biol Cell 8:2647-57. 1997
    ..Thus, mutation of integrin alpha4 "EF-hand-like" sites may impair 1) static cell adhesion and 2) adhesion strengthening under shear flow by a mechanism that does not involve alterations of initial ligand binding...
  3. ncbi request reprint Epitope mapping of antibodies to the C-terminal region of the integrin beta 2 subunit reveals regions that become exposed upon receptor activation
    C Lu
    Center for Blood Research, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 166:5629-37. 2001
    ..We thus define five different beta(2) stalk subregions, mAb binding to which correlates with effect on activation, and define regions in an interface that becomes exposed upon integrin activation...
  4. ncbi request reprint Ultrastructure and function of dimeric, soluble intercellular adhesion molecule-1 (ICAM-1)
    C D Jun
    Center for Blood Research and the Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 276:29019-27. 2001
    ..5--3-fold greater than that of monomeric ICAM-1. These studies demonstrate that ICAM-1 can form at least three different topologies and that dimerization at domain 1 does not interfere with binding in domain 1 to alpha(L)beta(2)...
  5. pmc A dimeric crystal structure for the N-terminal two domains of intercellular adhesion molecule-1
    J M Casasnovas
    The Center for Blood Research and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 95:4134-9. 1998
    ....
  6. pmc Reversibly locking a protein fold in an active conformation with a disulfide bond: integrin alphaL I domains with high affinity and antagonist activity in vivo
    M Shimaoka
    The Center for Blood Research and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 98:6009-14. 2001
    ..The ability to reversibly lock a protein fold in an active conformation with dramatically increased affinity opens vistas in therapeutics and proteomics...
  7. pmc Lymphocyte adhesion through very late antigen 4: evidence for a novel binding site in the alternatively spliced domain of vascular cell adhesion molecule 1 and an additional alpha 4 integrin counter-receptor on stimulated endothelium
    R H Vonderheide
    Department of Pathology, Harvard Medical School, Boston, Massachusetts
    J Exp Med 175:1433-42. 1992
    ..Time course experiments indicate that the fraction of alpha 4 integrin-dependent binding that can be blocked by anti-VCAM-1 mAb E1/6 rises and peaks within 2 h of tumor necrosis factor (TNF) stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)..
  8. ncbi request reprint Amino acid residues in the PSI domain and cysteine-rich repeats of the integrin beta2 subunit that restrain activation of the integrin alpha(X)beta(2)
    Q Zang
    Center for Blood Research, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 276:6922-9. 2001
    ..The opening of this interface is linked to structural rearrangements in other domains that activate ligand binding...
  9. ncbi request reprint Kinetic and mechanical basis of rolling through an integrin and novel Ca2+-dependent rolling and Mg2+-dependent firm adhesion modalities for the alpha 4 beta 7-MAdCAM-1 interaction
    M de Château
    The Center for Blood Research, Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
    Biochemistry 40:13972-9. 2001
    ....
  10. pmc Lymphocyte function-associated antigen-1 binding residues in intercellular adhesion molecule-2 (ICAM-2) and the integrin binding surface in the ICAM subfamily
    J M Casasnovas
    The Center for Blood Research and Harvard Medical School, Department of Pathology, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 96:3017-22. 1999
    ..The binding site on VCAM-1 includes the lower portion of domain 1 and the upper part of domain 2, whereas the LFA-1 binding site on ICAM is confined to the upper part of domain 1...
  11. ncbi request reprint C-terminal opening mimics 'inside-out' activation of integrin alpha5beta1
    J Takagi
    The Center for Blood Research, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Struct Biol 8:412-6. 2001
    ..These findings suggest that the overall mechanism for integrin inside-out activation involves the spatial separation of the cytoplasmic and/or transmembrane domains...
  12. ncbi request reprint The structure of immunoglobulin superfamily domains 1 and 2 of MAdCAM-1 reveals novel features important for integrin recognition
    K Tan
    Laboratory of Immunobiology Dana Farber Cancer Institute 44 Binney Street, Boston, MA 02115, USA
    Structure 6:793-801. 1998
    ....
  13. pmc An isolated, surface-expressed I domain of the integrin alphaLbeta2 is sufficient for strong adhesive function when locked in the open conformation with a disulfide bond
    C Lu
    The Center for Blood Research, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 98:2387-92. 2001
    ..These data establish the importance of conformational change in the alphaL I domain for adhesive function and show that this domain is sufficient for full adhesive activity...
  14. pmc Sequential regulation of alpha 4 beta 1 and alpha 5 beta 1 integrin avidity by CC chemokines in monocytes: implications for transendothelial chemotaxis
    C Weber
    Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Cell Biol 134:1063-73. 1996
    ..Transient activation and deactivation of VLA-4 may serve to facilitate transendothelial diapedesis, whereas late and prolonged activation of VLA-5 may mediate subsequent interactions with the basement membrane and extracellular matrix...
  15. ncbi request reprint The chemokine receptor CXCR4 is required for the retention of B lineage and granulocytic precursors within the bone marrow microenvironment
    Q Ma
    The Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Immunity 10:463-71. 1999
    ..Granulocytic cells are reduced in bone marrow but elevated and less mature in the blood. B lineage and granulocytic precursors are released into the periphery in absence of CXCR4...
  16. pmc Definition of EGF-like, closely interacting modules that bear activation epitopes in integrin beta subunits
    J Takagi
    Center for Blood Research and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 98:11175-80. 2001
    ..This arrangement is consistent with a tight intermodule connection, a prerequisite for signal propagation from the membrane to the ligand binding headpiece...
  17. pmc Dimerization and the effectiveness of ICAM-1 in mediating LFA-1-dependent adhesion
    C D Jun
    Center for Blood Research and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 98:6830-5. 2001
    ..These studies demonstrate that a single ICAM-1 monomer, not dimeric ICAM-1, represents the complete, "fully competent" LFA-1-binding surface...
  18. ncbi request reprint Modulation of endothelial cell adhesion by hevin, an acidic protein associated with high endothelial venules
    J P Girard
    Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 271:4511-7. 1996
    ..Hevin-treated cells do not form focal adhesions and exhibit a rounded morphology. Together, these results suggest that hevin is an abundant extracellular protein that modulates high endothelial cell adhesion to the basement membrane...
  19. ncbi request reprint The top of the inserted-like domain of the integrin lymphocyte function-associated antigen-1 beta subunit contacts the alpha subunit beta -propeller domain near beta-sheet 3
    Q Zang
    Center for Blood Research, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 275:22202-12. 2000
    ..YTA-1 preferentially reacts with activated LFA-1 and is a function-blocking antibody, suggesting that conformational movements occur near the interface it defines between the LFA-1 alpha and beta subunits...
  20. pmc Locking in alternate conformations of the integrin alphaLbeta2 I domain with disulfide bonds reveals functional relationships among integrin domains
    C Lu
    The Center for Blood Research, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 98:2393-8. 2001
    ..These results suggest that Mn(2+) activates alphaLbeta2 by binding to a site other than the I domain, most likely the I-like domain of beta2...
  21. ncbi request reprint Implications for familial hypercholesterolemia from the structure of the LDL receptor YWTD-EGF domain pair
    H Jeon
    Brigham Women s Hospital and Harvard Medical School Department of Pathology, 75 Francis Street, Boston, Massachusetts 02115, USA
    Nat Struct Biol 8:499-504. 2001
    ..A second subset of FH mutations are located at the interface between the propeller and the C-terminal EGF module, suggesting a structural requirement for maintaining the integrity of the interdomain interface...
  22. ncbi request reprint Crystal structure of ICAM-2 reveals a distinctive integrin recognition surface
    J M Casasnovas
    The Center for Blood Research, Harvard Medical School, Department of Pathology, Boston, Massachusetts 02115, USA
    Nature 387:312-5. 1997
    ..A model of ICAM-1 based on the ICAM-2 structure provides a framework for understanding its recognition by pathogens...
  23. ncbi request reprint On the species specificity of the interaction of LFA-1 with intercellular adhesion molecules
    S C Johnston
    Center for Blood Research, Boston, MA 02115
    J Immunol 145:1181-7. 1990
    ..Increased adhesiveness for ICAM-1 stimulated by phorbol esters could be demonstrated for hybrid LFA-1 molecules with human alpha and murine beta subunits...
  24. ncbi request reprint Differential requirements for LFA-1 binding to ICAM-1 and LFA-1-mediated cell aggregation
    L Petruzzelli
    Harvard Medical School, Center for Blood Research, Boston, MA 02115, USA
    J Immunol 160:4208-16. 1998
    ..By examining both ligand binding and aggregation, we have been able to dissect the signaling components critical in the multistep process of LFA-1-mediated cellular adhesion...
  25. pmc Selectin receptor-ligand bonds: Formation limited by shear rate and dissociation governed by the Bell model
    S Chen
    The Center for Blood Research, Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 98:950-5. 2001
    ..Cummings, R. D. & McEver, R. P. (1998) J. Biol. Chem. 273, 32506-32513]...
  26. ncbi request reprint Immunoaffinity chromatography
    T A Springer
    Center for Blood Research, Harvard Medical School, Boston, Massachussets, USA
    Curr Protoc Immunol . 2001
    ..The detergent octyl beta-D-glucoside can be used instead of Triton X-100 for elution. Because octyl beta-D-glucoside has a high critical micelle concentration (CMC), it can be readily removed by dialysis, as described...
  27. pmc Experimental support for a beta-propeller domain in integrin alpha-subunits and a calcium binding site on its lower surface
    C Oxvig
    Department of Pathology, The Center for Blood Research and Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 95:4870-5. 1998
    ..Thus, the region on the lower surface of the beta-propeller domain to which mAb CBRM1/20 binds does not bind ligand and, furthermore, cannot bind other integrin domains, such as those of the beta-subunit...
  28. pmc The integrin VLA-4 supports tethering and rolling in flow on VCAM-1
    R Alon
    Harvard Medical School, Department of Pathology, Boston, Massachusetts 02115
    J Cell Biol 128:1243-53. 1995
    ..These agents, and the alpha 4 cytoplasmic domain, promoted increased resistance to detachment. Together the results show that VLA-4 is a versatile integrin that can mediate tethering, rolling, and firm arrest on VCAM-1...
  29. pmc Intercellular adhesion molecule 3, a third adhesion counter-receptor for lymphocyte function-associated molecule 1 on resting lymphocytes
    A R de Fougerolles
    Department of Pathology, Harvard Medical School, Boston, Massachusetts
    J Exp Med 175:185-90. 1992
    ..In assays of adhesion of resting lymphocytes to purified LFA-1, ICAM-3 is by far the most functionally important ICAM, implying an important role for ICAM-3 in the generation of immune responses...
  30. pmc Rolling and transient tethering of leukocytes on antibodies reveal specializations of selectins
    S Chen
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 94:3172-7. 1997
    ....
  31. pmc Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice
    Q Ma
    The Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 95:9448-53. 1998
    ..This receptor-ligand selectivity is unusual among chemokines and their receptors, as is the function in migration of nonhematopoietic cells...
  32. ncbi request reprint Immunoaffinity chromatography
    T A Springer
    Center for Blood Research Harvard Medical School, Boston, Massachusetts, USA
    Curr Protoc Protein Sci . 2001
    ..The procedure for covalently linking an antibody to Sepharose using the cyanogen bromide activation method is given in a support protocol...
  33. ncbi request reprint 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...
  34. pmc Effector differentiation is not prerequisite for generation of memory cytotoxic T lymphocytes
    N Manjunath
    The Center for Blood Research, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 108:871-8. 2001
    ..In addition to providing a simple means to generate memory cells in virtually unlimited numbers, our results suggest that effector differentiation is not a prerequisite for memory cell generation...
  35. ncbi request reprint Association of the membrane proximal regions of the alpha and beta subunit cytoplasmic domains constrains an integrin in the inactive state
    C Lu
    Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 276:14642-8. 2001
    ..Our data demonstrate that cytoplasmic, membrane proximal association between integrin alpha and beta subunits, constrains an integrin in the inactive conformation...
  36. ncbi request reprint Expression of stromal-derived factor-1 is decreased by IL-1 and TNF and in dermal wound healing
    E R Fedyk
    Center for Blood Research, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 166:5749-54. 2001
    ..Levels of SDF-1 mRNA also decrease in acutely inflamed mouse dermal wounds. We propose that SDF-1 functions as a homeostatic regulator of tissue remodeling, whose expression stabilizes existing dermal architecture...
  37. pmc Cloning and expression of intercellular adhesion molecule 3 reveals strong homology to other immunoglobulin family counter-receptors for lymphocyte function-associated antigen 1
    A R de Fougerolles
    Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115
    J Exp Med 177:1187-92. 1993
    ..The five Ig-like domains of ICAM-3 are highly homologous with those of human ICAM-1 (52% identity) and human ICAM-2 (37% identity)...
  38. ncbi request reprint Intercellular adhesion molecule-1-deficient mice are less susceptible to cerebral ischemia-reperfusion injury
    S G Soriano
    Department of Anesthesia Children s Hospital, Boston, MA 02115, USA
    Ann Neurol 39:618-24. 1996
    ..These data support the premise that neutrophil adhesion in ischemic areas may be deleterious and that ICAM-1 deficiency reduces neurological damage after transient focal cerebral ischemia...
  39. ncbi request reprint Immunoaffinity chromatography
    T A Springer
    Center for Blood Research Harvard Medical School, Boston, Massachusetts, USA
    Curr Protoc Neurosci . 2001
    ..All these methods are described in this unit along with a procedure for covalently linking an antibody to Sepharose using the cyanogen bromide activation method...
  40. ncbi request reprint Functional expression of the CXC-chemokine receptor-4/fusin on mouse microglial cells and astrocytes
    S Tanabe
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 159:905-11. 1997
    ..In contrast, astrocytes did not migrate toward a gradient of SDF-1alpha. The failure of SDF-1alpha to induce astrocyte migration was specific, as another chemokine, macrophage inflammatory protein-1alpha, triggered astrocyte chemotaxis...
  41. ncbi request reprint Cloning and chromosomal localization of a novel gene-encoding a human beta 2-integrin alpha subunit
    D A Wong
    Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA
    Gene 171:291-4. 1996
    ..The ITGAD gene is highly homologous to the three previously known alpha subunit-encoding genes, that compose the beta 2 integrin family, in deduced amino acid sequence, intron/exon structure and mapping location (chromosome 16p11)...
  42. pmc A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1)
    C C Bleul
    The Center for Blood Research, Harvard Medical School, Department of Pathology, Boston, Massachusetts 02115, USA
    J Exp Med 184:1101-9. 1996
    ..Since SDF-1 is expressed constitutively in a broad range of tissues it may have a role in immune surveillance and in basal extravasation of lymphocytes and monocytes rather than in inflammation...
  43. ncbi request reprint Biology and physics of von Willebrand factor concatamers
    T A Springer
    Immune Disease Institute, Children s Hospital Boston, Boston, MA, USA
    J Thromb Haemost 9:130-43. 2011
    ..Single molecule studies on the A1-GPIb receptor-ligand bond demonstrate a specialised flex-bond that enhances resistance to the strong hydrodynamic forces experienced at sites of haemorrhage...
  44. ncbi request reprint Cloning from purified high endothelial venule cells of hevin, a close relative of the antiadhesive extracellular matrix protein SPARC
    J P Girard
    Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115, USA
    Immunity 2:113-23. 1995
    ..Hevin could contribute to the induction or maintenance of features of the HEV endothelium that facilitate lymphocyte migration...
  45. ncbi request reprint A binding interface on the I domain of lymphocyte function-associated antigen-1 (LFA-1) required for specific interaction with intercellular adhesion molecule 1 (ICAM-1)
    C Huang
    Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 270:19008-16. 1995
    ....
  46. ncbi request reprint ICAM-1 is required for T cell proliferation but not for anergy or apoptosis induced by Staphylococcus aureus enterotoxin B in vivo
    J A Gonzalo
    Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA
    Int Immunol 7:1691-8. 1995
    ..Interestingly, our study showed that SEB-induced proliferation of CD8+ V beta 8+ T cells from lymph nodes (not from spleen) is independent of the interactions mediated by ICAM-1...
  47. ncbi request reprint Immunoaffinity chromatography
    T A Springer
    Center for Blood Research, Harvard Medical School, Boston, Massachusetts, USA
    Curr Protoc Mol Biol . 2001
    ..An alternate protocol describes the use of batch purification of antigens which can shorten the column loading time...
  48. pmc Transition from rolling to firm adhesion can be mimicked by extension of integrin alphaLbeta2 in an intermediate affinity state
    Azucena Salas
    CBR Institute for Biomedical Research, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 281:10876-82. 2006
    ....
  49. pmc Directed evolution to probe protein allostery and integrin I domains of 200,000-fold higher affinity
    Moonsoo Jin
    The CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:5758-63. 2006
    ..The F265S/F292G mutant is potent in antagonizing lymphocyte function-associated antigen 1-dependent lymphocyte adhesion, aggregation, and transmigration...
  50. pmc Identification and characterization of a human monoclonal antagonistic antibody AL-57 that preferentially binds the high-affinity form of lymphocyte function-associated antigen-1
    Lili Huang
    Dyax Corporation, Cambridge, MA 02139, USA
    J Leukoc Biol 80:905-14. 2006
    ..These results indicate that specifically targeting the HA I domain is sufficient to inhibit LFA-1-mediated, adhesive functions. AL-57 represents a therapeutic candidate for treatment of inflammatory and autoimmune diseases...
  51. pmc Integrin structures and conformational signaling
    Bing Hao Luo
    The CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, 200 Longwood Ave, Boston, MA 02115, USA
    Curr Opin Cell Biol 18:579-86. 2006
    ....
  52. pmc Rational design of intercellular adhesion molecule-1 (ICAM-1) variants for antagonizing integrin lymphocyte function-associated antigen-1-dependent adhesion
    Gang Song
    CBR Institute for Biomedical Research, and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 281:5042-9. 2006
    ..Thus, rational design can be used to engineer novel adhesion molecules with high monomeric affinity; furthermore, the ICAM-1 mutant holds promise for targeting LFA-1-ICAM-1 interaction for biological studies and therapeutic purposes...
  53. pmc Regulation of outside-in signaling and affinity by the beta2 I domain of integrin alphaLbeta2
    JianFeng Chen
    CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:13062-7. 2006
    ..Furthermore, ADMIDAS mutation abolished spreading on ligand-bearing substrates. Thus, beta(2) I domain metal ion-binding sites regulate alpha(L) I domain affinity, and the ADMIDAS is required for outside-in signaling...
  54. pmc Exposure of acidic residues as a danger signal for recognition of fibrinogen and other macromolecules by integrin alphaXbeta2
    Thomas Vorup-Jensen
    Center for Blood Research Institute for Biomedical Research, and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:1614-9. 2005
    ..The observations suggest that the pericellular proteolysis at the leading edge of neutrophils not only facilitates passage through the extracellular matrix but also manufactures binding sites for alphaXbeta2...
  55. pmc The primacy of affinity over clustering in regulation of adhesiveness of the integrin {alpha}L{beta}2
    Minsoo Kim
    The CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    J Cell Biol 167:1241-53. 2004
    ..Thus, LFA-1 clustering does not precede ligand binding, and instead functions in adhesion strengthening after binding to multivalent ligands...
  56. ncbi request reprint Contribution of N-linked glycans to the conformation and function of intercellular adhesion molecules (ICAMs)
    David Jimenez
    Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas, Campus Universidad Autonoma, 28049 Madrid, Spain
    J Biol Chem 280:5854-61. 2005
    ..N-Linked glycosylation regulate both conformation and immune related functions of ICAM receptors...
  57. ncbi request reprint Therapeutic antagonists and the conformational regulation of the beta2 integrins
    Motomu Shimaoka
    The CBR Institute for Biomedical Research, Department of Anesthesia and Pathology, Harvard Medical School, 200 Longwood, Boston, MA 02115, USA
    Curr Top Med Chem 4:1485-95. 2004
    ..The small molecule antagonists to the beta2 integrin highlight the importance of the structural linkages within and between integrin domains for transmission of the conformational signals and regulation of the overall conformation...
  58. ncbi request reprint The three-dimensional structure of integrins and their ligands, and conformational regulation of cell adhesion
    Timothy A Springer
    CBR Institute for Biomedical Research, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Adv Protein Chem 68:29-63. 2004
    ....
  59. ncbi request reprint RIAM, an Ena/VASP and Profilin ligand, interacts with Rap1-GTP and mediates Rap1-induced adhesion
    Esther M Lafuente
    Department of Medical Oncology, Dana Farber Cancer Institute, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Dev Cell 7:585-95. 2004
    ..RIAM knockdown displaced Rap1-GTP from the plasma membrane and abrogated Rap1-induced adhesion. Thus, RIAM links Rap1 to integrin activation and plays a role in regulating actin dynamics...
  60. pmc AL-57, a ligand-mimetic antibody to integrin LFA-1, reveals chemokine-induced affinity up-regulation in lymphocytes
    Motomu Shimaoka
    CBR Institute for Biomedical Research and Department of Anesthesia, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:13991-6. 2006
    ..Affinity up-regulation correlates with global conformational changes of LFA-1 to the extended form. Affinity increase stimulated by CXCL-12 is transient and peaks 2 to 5 min after stimulation...
  61. pmc A small molecule agonist of an integrin, alphaLbeta2
    Wei Yang
    CBR Institute for Biomedical Research, Departments of Pathology and Anesthesia, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 281:37904-12. 2006
    ..Agonism by compound 4 results in accumulation of alpha(L)beta(2) in the uropod, extreme uropod elongation, and defective de-adhesion. Small molecule integrin agonists open up novel therapeutic possibilities...
  62. ncbi request reprint Activation of leukocyte beta2 integrins by conversion from bent to extended conformations
    Noritaka Nishida
    CBR Institute for Biomedical Research, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
    Immunity 25:583-94. 2006
    ..The results establish an intimate relationship between extension of beta(2) integrins and their activation in immune responses and leukocyte trafficking...
  63. pmc An unusual allosteric mobility of the C-terminal helix of a high-affinity alphaL integrin I domain variant bound to ICAM-5
    Hongmin Zhang
    Department of Medical Oncology and Department of Cancer Biology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Mol Cell 31:432-7. 2008
    ..This remarkable feature allows the alpha7 helix to trigger integrin's large-scale conformational changes with little energy penalty. It serves as a mechanistic example of how a weakly bound adhesion molecule works in signaling...
  64. pmc Trans-cellular migration: cell-cell contacts get intimate
    Christopher V Carman
    Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    Curr Opin Cell Biol 20:533-40. 2008
    ....
  65. pmc Nonmuscle myosin heavy chain IIA mediates integrin LFA-1 de-adhesion during T lymphocyte migration
    Nicole A Morin
    Department of Surgery, Rhode Island Hospital and Brown Medical School, Providence, RI 02903, USA
    J Exp Med 205:195-205. 2008
    ..Thus, during T lymphocyte migration, uropodal adhesion depends on LFA-1 avidity, where MyH9 serves as a key mechanical link between LFA-1 and the cytoskeleton that is critical for LFA-1 de-adhesion...
  66. pmc Structural plasticity in Ig superfamily domain 4 of ICAM-1 mediates cell surface dimerization
    Xuehui Chen
    Immune Disease Institute, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 104:15358-63. 2007
    ..Overall, the studies reveal that monomer-dimer transition is associated with a surprisingly large, physiologically relevant, IgSF domain rearrangement...
  67. pmc Specific and covalent labeling of a membrane protein with organic fluorochromes and quantum dots
    Roberto Bonasio
    The CBR Institute for Biomedical Research, Inc, Department of Pathology, Harvard Medical School, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 104:14753-8. 2007
    ..The availability of a genetically encoded tag that binds covalently to quantum dots could foster the development of new experimental strategies for the study of protein dynamics in vivo...
  68. ncbi request reprint Binding between the integrin alphaXbeta2 (CD11c/CD18) and heparin
    Thomas Vorup-Jensen
    Immune Disease Institute formerly CBR Institute for Biomedical Research, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 282:30869-77. 2007
    ..Furthermore, the fully sulfated heparin fragment induced conformational change in the ectodomain of the alphaXbeta2 receptor, also demonstrating allosteric linkage between heparin binding and integrin conformation...
  69. pmc Requirement of alpha and beta subunit transmembrane helix separation for integrin outside-in signaling
    Jieqing Zhu
    The CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Blood 110:2475-83. 2007
    ..This defect was rescued by reduction of the disulfide bond. Our results demonstrate that the separation of transmembrane domains is required for integrin outside-in signal transduction...
  70. pmc Transcellular diapedesis is initiated by invasive podosomes
    Christopher V Carman
    The CBR Institute for Biomedical Research, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Immunity 26:784-97. 2007
    ..These findings provide insights into basic mechanisms for leukocyte trafficking and the functions of podosomes...
  71. pmc Tests of the extension and deadbolt models of integrin activation
    Jieqing Zhu
    The CBR Institute for Biomedical Research, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 282:11914-20. 2007
    ..The data demonstrate that integrin extension is required for ligand binding during integrin inside-out signaling and that the deadbolt does not regulate integrin activation...
  72. 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
    ..In this review, we focus on integrin structure as it relates to affinity modulation, ligand binding, outside-in signaling, and cell surface distribution dynamics...
  73. pmc Importance of force linkage in mechanochemistry of adhesion receptors
    Nathan S Astrof
    The CBR Institute for Biomedical Research, Department of Anesthesia and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Biochemistry 45:15020-8. 2006
    ....
  74. pmc Complement and the multifaceted functions of VWA and integrin I domains
    Timothy A Springer
    CBR Institute for Biomedical Research and Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
    Structure 14:1611-6. 2006
    ..Finally, implications for metastability of complement convertases are discussed...
  75. pmc Disrupting integrin transmembrane domain heterodimerization increases ligand binding affinity, not valency or clustering
    Bing Hao Luo
    The CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:3679-84. 2005
    ..Our studies provide evidence that disrupting the integrin heterodimeric TM helix-helix interface activates ligand binding mainly by increasing the monomeric affinity for ligand, but not the receptor valency, i.e., clustering...
  76. ncbi request reprint The relative influence of metal ion binding sites in the I-like domain and the interface with the hybrid domain on rolling and firm adhesion by integrin alpha4beta7
    JianFeng Chen
    The CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    J Biol Chem 279:55556-61. 2004
    ..Overall, the results demonstrate the importance of headpiece allostery in the conversion of rolling to firm adhesion...
  77. ncbi request reprint Structural basis for allostery in integrins and binding to fibrinogen-mimetic therapeutics
    Tsan Xiao
    The CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 432:59-67. 2004
    ..Allostery in the head thus disrupts interaction between the legs in a previously described low-affinity bent integrin conformation, and leg extension positions the high-affinity head far above the cell surface...
  78. pmc Stabilizing the open conformation of the integrin headpiece with a glycan wedge increases affinity for ligand
    Bing Hao Luo
    Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:2403-8. 2003
    ....
  79. ncbi request reprint High affinity ligand binding by integrins does not involve head separation
    Bing Hao Luo
    Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 278:17185-9. 2003
    ..The mechanisms of conformational regulation of integrin function should therefore be considered in the context of the associated alphabeta headpiece...
  80. pmc Structure and allosteric regulation of the alpha X beta 2 integrin I domain
    Thomas Vorup-Jensen
    Center for Blood Research, Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:1873-8. 2003
    ..Gel permeation chromatography supported a conformational change between the wild-type and mutated domains. Conservation of allosteric regulation in the alpha X I domain points to the functional importance of this phenomenon...
  81. ncbi request reprint Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation
    Motomu Shimaoka
    The Center for Blood Research, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Cell 112:99-111. 2003
    ..Pulling down on the C-terminal alpha 7 helix with introduced disulfide bonds ratchets the beta 6-alpha 7 loop into three different positions in the closed, intermediate, and open conformations, with a progressive increase in affinity...
  82. ncbi request reprint Predicted and experimental structures of integrins and beta-propellers
    Timothy A Springer
    Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Curr Opin Struct Biol 12:802-13. 2002
    ..Recently determined structures show remarkable successes, especially with beta-propeller domain predictions, and also reveal how ligand binding by integrins is conformationally regulated...
  83. pmc Stabilizing the integrin alpha M inserted domain in alternative conformations with a range of engineered disulfide bonds
    Motomu Shimaoka
    Center for Blood Research, Departments of Pathology, Pediatrics, and Anesthesia, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:16737-41. 2002
    ..By contrast, a disulfide stabilizing the closed conformation resulted in inactive alphaMbeta2 that was resistant to activation but became activatable after dithiothreitol treatment...
  84. ncbi request reprint Integrin activation and structural rearrangement
    Junichi Takagi
    The Center for Blood Research, Department of Pathology, Harvard Medical School, Boston 02115, Massachusetts, USA
    Immunol Rev 186:141-63. 2002
    ....
  85. ncbi request reprint Global conformational rearrangements in integrin extracellular domains in outside-in and inside-out signaling
    Junichi Takagi
    The Center for Blood Research, Departments of Pathology and Pediatrics, Harvard Medical School, Boston, MA 02115, USA
    Cell 110:599-11. 2002
    ..Breakage of a C-terminal clasp between the alpha and beta subunits enhances Mn(2+)-induced unbending and ligand binding...
  86. ncbi request reprint César Milstein, the father of modern immunology
    Timothy A Springer
    Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA
    Nat Immunol 3:501-3. 2002
  87. ncbi request reprint Immunology. Retrospective: César Milstein (1927-2002)
    Timothy A Springer
    Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA
    Science 296:1253. 2002
  88. ncbi request reprint Conformational regulation of integrin structure and function
    Motomu Shimaoka
    The Center for Blood Research, Department of Pathology and Anesthesia, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Annu Rev Biophys Biomol Struct 31:485-516. 2002
    ....
  89. ncbi request reprint The role of the specificity-determining loop of the integrin beta subunit I-like domain in autonomous expression, association with the alpha subunit, and ligand binding
    Junichi Takagi
    The Center for Blood Research and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
    Biochemistry 41:4339-47. 2002
    ....
  90. ncbi request reprint Cysteine-rich module structure reveals a fulcrum for integrin rearrangement upon activation
    Natalia Beglova
    Department of Pathology, Harvard Medical School, 75 Francis St, Boston, Masschusetts 02115, USA
    Nat Struct Biol 9:282-7. 2002
    ....
  91. ncbi request reprint Activation-induced conformational changes in the I domain region of lymphocyte function-associated antigen 1
    Qing Ma
    Department of Pathology, Center for Blood Research and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 277:10638-41. 2002
    ..Our data demonstrate that these two regions undergo significant conformational changes during LFA-1 activation and that the I domain of activated LFA-1 adopts a similar tertiary structure as the predicted locked open form...
  92. pmc The critical cytoplasmic regions of the alphaL/beta2 integrin in Rap1-induced adhesion and migration
    Yumi Tohyama
    Department of Molecular Immunology and Allergy, Graduate School of Medicine, Kyoto University, Japan
    Mol Biol Cell 14:2570-82. 2003
    ..Our study revealed novel requirements of amino acid residues of the LFA-1 cytoplasmic region in the response to the inside-out signaling and the subsequent deadhesion process...
  93. ncbi request reprint Complex between nidogen and laminin fragments reveals a paradigmatic beta-propeller interface
    Junichi Takagi
    The Center for Blood Research, Boston, Massachusetts 02115, USA
    Nature 424:969-74. 2003
    ....
  94. pmc Structure of integrin alpha5beta1 in complex with fibronectin
    Junichi Takagi
    The Center for Blood Research, Department of Pediatrics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    EMBO J 22:4607-15. 2003
    ..This finding is corroborated by kinetic analysis of real-time binding data, which shows that the synergy site greatly enhances k(on) but has little effect on the stability or k(off) of the complex...
  95. ncbi request reprint The binding sites for competitive antagonistic, allosteric antagonistic, and agonistic antibodies to the I domain of integrin LFA-1
    Chafen Lu
    CBR Institute for Biomedical Research, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 173:3972-8. 2004
    ..5 angstroms; maximum, 1.0 angstroms). Agonism by this mAb is thus likely to result from altering the orientation of the I domain with respect to other domains within an intact integrin alphaLbeta2 heterodimer...
  96. pmc Integrin beta3 regions controlling binding of murine mAb 7E3: implications for the mechanism of integrin alphaIIbbeta3 activation
    Andrea Artoni
    Laboratory of Blood and Vascular Biology, The Rockefeller University, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 101:13114-20. 2004
    ..Thus, our data are consistent with alphaIIbbeta3 existing in variably bent conformations in equilibrium with each other on unactivated platelets, and activation resulting in alphaIIbbeta3 adopting a more extended conformation...
  97. pmc A specific interface between integrin transmembrane helices and affinity for ligand
    Bing Hao Luo
    Center for Blood Research, Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA
    PLoS Biol 2:e153. 2004
    ....
  98. ncbi request reprint Allosteric beta1 integrin antibodies that stabilize the low affinity state by preventing the swing-out of the hybrid domain
    Bing Hao Luo
    The CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 279:27466-71. 2004
    ....
  99. ncbi request reprint Structural basis for dimerization of ICAM-1 on the cell surface
    Yuting Yang
    Dana Farber Cancer Institute, Boston, MA 02115, USA
    Mol Cell 14:269-76. 2004
    ....
  100. ncbi request reprint Rolling adhesion through an extended conformation of integrin alphaLbeta2 and relation to alpha I and beta I-like domain interaction
    Azucena Salas
    The CBR Institute for Biomedical Research, Department of Pathology, 200 Longwood Avenue, Boston, MA 02115 USA
    Immunity 20:393-406. 2004
    ....
  101. pmc Activation of integrin beta-subunit I-like domains by one-turn C-terminal alpha-helix deletions
    Wei Yang
    CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 101:2333-8. 2004
    ....