Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 19 September 2003:
Vol. 301. no. 5640, pp. 1720 - 1725
DOI: 10.1126/science.1084174
Prev | Table of Contents | Next

Reports

Bidirectional Transmembrane Signaling by Cytoplasmic Domain Separation in Integrins

Minsoo Kim,* Christopher V. Carman,* Timothy A. Springer{dagger}

Although critical for development, immunity, wound healing, and metastasis, integrins represent one of the few classes of plasma membrane receptors for which the basic signaling mechanism remains a mystery. We investigated cytoplasmic conformational changes in the integrin LFA-1 ({alpha}Lß2) in living cells by measuring fluorescence resonance energy transfer between cyan fluorescent protein–fused and yellow fluorescent protein–fused {alpha}L and ß2 cytoplasmic domains. In the resting state these domains were close to each other, but underwent significant spatial separation upon either intracellular activation of integrin adhesiveness (inside-out signaling) or ligand binding (outside-in signaling). Thus, bidirectional integrin signaling is accomplished by coupling extracellular conformational changes to an unclasping and separation of the {alpha} and ß cytoplasmic domains, a distinctive mechanism for transmitting information across the plasma membrane.

CBR Institute for Biomedical Research, Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.



* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: springeroffice{at}cbr.med.harvard.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
New PI(4,5)P2- and membrane proximal integrin-binding motifs in the talin head control {beta}3-integrin clustering.
F. Saltel, E. Mortier, V. P. Hytonen, M.-C. Jacquier, P. Zimmermann, V. Vogel, W. Liu, and B. Wehrle-Haller (2009)
J. Cell Biol. 187, 715-731
   Abstract »    Full Text »    PDF »
Mechanisms underlying neutrophil-mediated monocyte recruitment.
O. Soehnlein, L. Lindbom, and C. Weber (2009)
Blood 114, 4613-4623
   Abstract »    Full Text »    PDF »
The CEACAM1 N-terminal Ig domain mediates cis- and trans-binding and is essential for allosteric rearrangements of CEACAM1 microclusters.
E. Klaile, O. Vorontsova, K. Sigmundsson, M. M. Muller, B. B. Singer, L.-G. Ofverstedt, S. Svensson, U. Skoglund, and B. Obrink (2009)
J. Cell Biol. 187, 553-567
   Abstract »    Full Text »    PDF »
Homophilic adhesion and CEACAM1-S regulate dimerization of CEACAM1-L and recruitment of SHP-2 and c-Src.
M. M. Muller, E. Klaile, O. Vorontsova, B. B. Singer, and B. Obrink (2009)
J. Cell Biol. 187, 569-581
   Abstract »    Full Text »    PDF »
Outside-In Signal Transmission by Conformational Changes in Integrin Mac-1.
C. T. Lefort, Y.-M. Hyun, J. B. Schultz, F.-Y. Law, R. E. Waugh, P. A. Knauf, and M. Kim (2009)
J. Immunol. 183, 6460-6468
   Abstract »    Full Text »    PDF »
LFA-1 Antagonists as Agents Limiting Human Immunodeficiency Virus Type 1 Infection and Transmission and Potentiating the Effect of the Fusion Inhibitor T-20.
M. R. Tardif, C. Gilbert, S. Thibault, J.-F. Fortin, and M. J. Tremblay (2009)
Antimicrob. Agents Chemother. 53, 4656-4666
   Abstract »    Full Text »    PDF »
Src Homology 2-Domain Containing Leukocyte-Specific Phosphoprotein of 76 kDa Is Mandatory for TCR-Mediated Inside-Out Signaling, but Dispensable for CXCR4-Mediated LFA-1 Activation, Adhesion, and Migration of T Cells.
J. Horn, X. Wang, P. Reichardt, T. E. Stradal, N. Warnecke, L. Simeoni, M. Gunzer, D. Yablonski, B. Schraven, and S. Kliche (2009)
J. Immunol. 183, 5756-5767
   Abstract »    Full Text »    PDF »
Structure of an integrin {alpha}IIb{beta}3 transmembrane-cytoplasmic heterocomplex provides insight into integrin activation.
J. Yang, Y.-Q. Ma, R. C. Page, S. Misra, E. F. Plow, and J. Qin (2009)
PNAS 106, 17729-17734
   Abstract »    Full Text »    PDF »
Crystal structure of the complete integrin {alpha}V{beta}3 ectodomain plus an {alpha}/{beta} transmembrane fragment.
J.-P. Xiong, B. Mahalingham, J. L. Alonso, L. A. Borrelli, X. Rui, S. Anand, B. T. Hyman, T. Rysiok, D. Muller-Pompalla, S. L. Goodman, et al. (2009)
J. Cell Biol. 186, 589-600
   Abstract »    Full Text »    PDF »
Cluster size regulates protein sorting in the immunological synapse.
N. C. Hartman, J. A. Nye, and J. T. Groves (2009)
PNAS 106, 12729-12734
   Abstract »    Full Text »    PDF »
Activated Integrin VLA-4 Localizes to the Lamellipodia and Mediates T Cell Migration on VCAM-1.
Y.-M. Hyun, H.-L. Chung, J. L. McGrath, R. E. Waugh, and M. Kim (2009)
J. Immunol. 183, 359-369
   Abstract »    Full Text »    PDF »
Cytohesin-1 controls the activation of RhoA and modulates integrin-dependent adhesion and migration of dendritic cells.
T. Quast, B. Tappertzhofen, C. Schild, J. Grell, N. Czeloth, R. Forster, R. Alon, L. Fraemohs, K. Dreck, C. Weber, et al. (2009)
Blood 113, 5801-5810
   Abstract »    Full Text »    PDF »
The Tail of Integrins, Talin, and Kindlins.
M. Moser, K. R. Legate, R. Zent, and R. Fassler (2009)
Science 324, 895-899
   Abstract »    Full Text »    PDF »
LFA-1 Affinity Regulation Is Necessary for the Activation and Proliferation of Naive T Cells.
Y. Wang, D. Li, R. Nurieva, J. Yang, M. Sen, R. Carreno, S. Lu, B. W. McIntyre, J. J. Molldrem, G. B. Legge, et al. (2009)
J. Biol. Chem. 284, 12645-12653
   Abstract »    Full Text »    PDF »
Interactions of platelet integrin {alpha}IIb and {beta}3 transmembrane domains in mammalian cell membranes and their role in integrin activation.
C. Kim, T.-L. Lau, T. S. Ulmer, and M. H. Ginsberg (2009)
Blood 113, 4747-4753
   Abstract »    Full Text »    PDF »
Antithrombotic effects of targeting {alpha}IIb{beta}3 signaling in platelets.
A. J. Ablooglu, J. Kang, B. G. Petrich, M. H. Ginsberg, and S. J. Shattil (2009)
Blood 113, 3585-3592
   Abstract »    Full Text »    PDF »
Migfilin, a Molecular Switch in Regulation of Integrin Activation.
S. S. Ithychanda, M. Das, Y.-Q. Ma, K. Ding, X. Wang, S. Gupta, C. Wu, E. F. Plow, and J. Qin (2009)
J. Biol. Chem. 284, 4713-4722
   Abstract »    Full Text »    PDF »
Rationally Designed Integrin {beta}3 Mutants Stabilized in the High Affinity Conformation.
B.-H. Luo, J. Karanicolas, L. D. Harmacek, D. Baker, and T. A. Springer (2009)
J. Biol. Chem. 284, 3917-3924
   Abstract »    Full Text »    PDF »
NMR Solution Conformations and Interactions of Integrin {alpha}L{beta}2 Cytoplasmic Tails.
A. Bhunia, X.-Y. Tang, H. Mohanram, S.-M. Tan, and S. Bhattacharjya (2009)
J. Biol. Chem. 284, 3873-3884
   Abstract »    Full Text »    PDF »
Disruption of the Integrin {alpha}L{beta}2 Transmembrane Domain Interface by {beta}2 Thr-686 Mutation Activates {alpha}L{beta}2 and Promotes Micro-clustering of the {alpha}L Subunits.
A. Vararattanavech, X. Lin, J. Torres, and S.-M. Tan (2009)
J. Biol. Chem. 284, 3239-3249
   Abstract »    Full Text »    PDF »
Linking integrin conformation to function.
J. A. Askari, P. A. Buckley, A. P. Mould, and M. J. Humphries (2009)
J. Cell Sci. 122, 165-170
   Abstract »    Full Text »    PDF »
Mechanisms that regulate adaptor binding to {beta}-integrin cytoplasmic tails.
K. R. Legate and R. Fassler (2009)
J. Cell Sci. 122, 187-198
   Abstract »    Full Text »    PDF »
Integrins in cell migration - the actin connection.
M. Vicente-Manzanares, C. K. Choi, and A. R. Horwitz (2009)
J. Cell Sci. 122, 199-206
   Abstract »    Full Text »    PDF »
A Dual Role for Talin in NK Cell Cytotoxicity: Activation of LFA-1-Mediated Cell Adhesion and Polarization of NK Cells.
E. M. Mace, S. J. Monkley, D. R. Critchley, and F. Takei (2009)
J. Immunol. 182, 948-956
   Abstract »    Full Text »    PDF »
JAM-L-mediated leukocyte adhesion to endothelial cells is regulated in cis by {alpha}4{beta}1 integrin activation.
A.-C. Luissint, P. G. Lutz, D. A. Calderwood, P.-O. Couraud, and S. Bourdoulous (2008)
J. Cell Biol. 183, 1159-1173
   Abstract »    Full Text »    PDF »
Transmigration of Neutrophils across Inflamed Endothelium Is Signaled through LFA-1 and Src Family Kinase.
M. R. Sarantos, H. Zhang, U. Y. Schaff, N. Dixit, H. N. Hayenga, C. A. Lowell, and S. I. Simon (2008)
J. Immunol. 181, 8660-8669
   Abstract »    Full Text »    PDF »
Mechanisms and consequences of agonist-induced talin recruitment to platelet integrin {alpha}IIb{beta}3.
N. Watanabe, L. Bodin, M. Pandey, M. Krause, S. Coughlin, V. A. Boussiotis, M. H. Ginsberg, and S. J. Shattil (2008)
J. Cell Biol. 181, 1211-1222
   Abstract »    Full Text »    PDF »
Functional analysis of the cytoplasmic domain of the integrin {alpha}1 subunit in endothelial cells.
T. D. Abair, N. Bulus, C. Borza, M. Sundaramoorthy, R. Zent, and A. Pozzi (2008)
Blood 112, 3242-3254
   Abstract »    Full Text »    PDF »
Kindlin-2 (Mig-2): a co-activator of {beta}3 integrins.
Y.-Q. Ma, J. Qin, C. Wu, and E. F. Plow (2008)
J. Cell Biol. 181, 439-446
   Abstract »    Full Text »    PDF »
Urokinase-type Plasminogen Activator Receptor Induces Conformational Changes in the Integrin {alpha}M{beta}2 Headpiece and Reorientation of Its Transmembrane Domains.
M.-L. Tang, A. Vararattanavech, and S.-M. Tan (2008)
J. Biol. Chem. 283, 25392-25403
   Abstract »    Full Text »    PDF »
{beta}2 integrin phosphorylation on Thr758 acts as a molecular switch to regulate 14-3-3 and filamin binding.
H. Takala, E. Nurminen, S. M. Nurmi, M. Aatonen, T. Strandin, M. Takatalo, T. Kiema, C. G. Gahmberg, J. Ylanne, and S. C. Fagerholm (2008)
Blood 112, 1853-1862
   Abstract »    Full Text »    PDF »
Regulation of integrin activation through the B-cell receptor.
E. Arana, N. E. Harwood, and F. D. Batista (2008)
J. Cell Sci. 121, 2279-2286
   Abstract »    Full Text »    PDF »
Talin at a glance.
D. R. Critchley and A. R. Gingras (2008)
J. Cell Sci. 121, 1345-1347
   Full Text »    PDF »
A Mechanism for Antibody-mediated Outside-in Activation of LFA-1.
R. Carreno, D. Li, M. Sen, I. Nira, T. Yamakawa, Q. Ma, and G. B. Legge (2008)
J. Biol. Chem. 283, 10642-10648
   Abstract »    Full Text »    PDF »
Intercellular Adhesion Molecule-3 Binding of Integrin {alpha}L{beta}2 Requires Both Extension and Opening of the Integrin Headpiece.
X.-Y. Tang, Y.-F. Li, and S.-M. Tan (2008)
J. Immunol. 180, 4793-4804
   Abstract »    Full Text »    PDF »
Regulation of LFA-1-dependent inflammatory cell recruitment by Cbl-b and 14-3-3 proteins.
E. Y. Choi, V. V. Orlova, S. C. Fagerholm, S. M. Nurmi, L. Zhang, C. M. Ballantyne, C. G. Gahmberg, and T. Chavakis (2008)
Blood 111, 3607-3614
   Abstract »    Full Text »    PDF »
The N-terminal Domains of Talin Cooperate with the Phosphotyrosine Binding-like Domain to Activate {beta}1 and {beta}3 Integrins.
M. Bouaouina, Y. Lad, and D. A. Calderwood (2008)
J. Biol. Chem. 283, 6118-6125
   Abstract »    Full Text »    PDF »
RhoA Is Involved in LFA-1 Extension Triggered by CXCL12 but Not in a Novel Outside-In LFA-1 Activation Facilitated by CXCL9.
R. Pasvolsky, V. Grabovsky, C. Giagulli, Z. Shulman, R. Shamri, S. W. Feigelson, C. Laudanna, and R. Alon (2008)
J. Immunol. 180, 2815-2823
   Abstract »    Full Text »    PDF »
Quantification of integrin receptor agonism by fluorescence lifetime imaging.
M. Parsons, A. J. Messent, J. D. Humphries, N. O. Deakin, and M. J. Humphries (2008)
J. Cell Sci. 121, 265-271
   Abstract »    Full Text »    PDF »
Nonmuscle myosin heavy chain IIA mediates integrin LFA-1 de-adhesion during T lymphocyte migration.
N. A. Morin, P. W. Oakes, Y.-M. Hyun, D. Lee, Y. E. Chin, M. R. King, T. A. Springer, M. Shimaoka, J. X. Tang, J. S. Reichner, et al. (2008)
J. Exp. Med. 205, 195-205
   Abstract »    Full Text »    PDF »
A Structural Hypothesis for the Transition between Bent and Extended Conformations of the Leukocyte beta2 Integrins.
M. Shi, S. Y. Foo, S.-M. Tan, E. P. Mitchell, S. K. A. Law, and J. Lescar (2007)
J. Biol. Chem. 282, 30198-30206
   Abstract »    Full Text »    PDF »
Requirement of {alpha} and {beta} subunit transmembrane helix separation for integrin outside-in signaling.
J. Zhu, C. V. Carman, M. Kim, M. Shimaoka, T. A. Springer, and B.-H. Luo (2007)
Blood 110, 2475-2483
   Abstract »    Full Text »    PDF »
Structural plasticity in Ig superfamily domain 4 of ICAM-1 mediates cell surface dimerization.
X. Chen, T. D. Kim, C. V. Carman, L.-Z. Mi, G. Song, and T. A. Springer (2007)
PNAS 104, 15358-15363
   Abstract »    Full Text »    PDF »
Specific and covalent labeling of a membrane protein with organic fluorochromes and quantum dots.
R. Bonasio, C. V. Carman, E. Kim, P. T. Sage, K. R. Love, T. R. Mempel, T. A. Springer, and U. H. von Andrian (2007)
PNAS 104, 14753-14758
   Abstract »    Full Text »    PDF »
Talin 1 and Paxillin Facilitate Distinct Steps in Rapid VLA-4-mediated Adhesion Strengthening to Vascular Cell Adhesion Molecule 1.
E. Manevich, V. Grabovsky, S. W. Feigelson, and R. Alon (2007)
J. Biol. Chem. 282, 25338-25348
   Abstract »    Full Text »    PDF »
The Cytosolic Protein Talin Induces an Intermediate Affinity Integrin {alpha}Lbeta2.
Y.-F. Li, R.-H. Tang, K.-J. Puan, S. K. A. Law, and S.-M. Tan (2007)
J. Biol. Chem. 282, 24310-24319
   Abstract »    Full Text »    PDF »
The MIG-2/Integrin Interaction Strengthens Cell-Matrix Adhesion and Modulates Cell Motility.
X. Shi, Y.-Q. Ma, Y. Tu, K. Chen, S. Wu, K. Fukuda, J. Qin, E. F. Plow, and C. Wu (2007)
J. Biol. Chem. 282, 20455-20466
   Abstract »    Full Text »    PDF »
A LAD-III syndrome is associated with defective expression of the Rap-1 activator CalDAG-GEFI in lymphocytes, neutrophils, and platelets.
R. Pasvolsky, S. W. Feigelson, S. S. Kilic, A. J. Simon, G. Tal-Lapidot, V. Grabovsky, J. R. Crittenden, N. Amariglio, M. Safran, A. M. Graybiel, et al. (2007)
J. Exp. Med. 204, 1571-1582
   Abstract »    Full Text »    PDF »
Tests of the Extension and Deadbolt Models of Integrin Activation.
J. Zhu, B. Boylan, B.-H. Luo, P. J. Newman, and T. A. Springer (2007)
J. Biol. Chem. 282, 11914-11920
   Abstract »    Full Text »    PDF »
Selective gene silencing in activated leukocytes by targeting siRNAs to the integrin lymphocyte function-associated antigen-1.
D. Peer, P. Zhu, C. V. Carman, J. Lieberman, and M. Shimaoka (2007)
PNAS 104, 4095-4100
   Abstract »    Full Text »    PDF »
An Essential Role for Talin during {alpha}Mbeta2-mediated Phagocytosis.
J. Lim, A. Wiedemann, G. Tzircotis, S. J. Monkley, D. R. Critchley, and E. Caron (2007)
Mol. Biol. Cell 18, 976-985
   Abstract »    Full Text »    PDF »
Phosphorylation of the LFA-1 Integrin beta2-Chain on Thr-758 Leads to Adhesion, Rac-1/Cdc42 Activation, and Stimulation of CD69 Expression in Human T Cells.
S. M. Nurmi, M. Autero, A. K. Raunio, C. G. Gahmberg, and S. C. Fagerholm (2007)
J. Biol. Chem. 282, 968-975
   Abstract »    Full Text »    PDF »
IpaA Targets beta1 Integrins and Rho to Promote Actin Cytoskeleton Rearrangements Necessary for Shigella Entry.
K. A. DeMali, A. L. Jue, and K. Burridge (2006)
J. Biol. Chem. 281, 39534-39541
   Abstract »    Full Text »    PDF »
A Small Molecule Agonist of an Integrin, {alpha}Lbeta2.
W. Yang, C. V. Carman, M. Kim, A. Salas, M. Shimaoka, and T. A. Springer (2006)
J. Biol. Chem. 281, 37904-37912
   Abstract »    Full Text »    PDF »
Activation of Platelet {alpha}IIbbeta3 by an Exogenous Peptide Corresponding to the Transmembrane Domain of {alpha}IIb.
H. Yin, R. I. Litvinov, G. Vilaire, H. Zhu, W. Li, G. A. Caputo, D. T. Moore, J. D. Lear, J. W. Weisel, W. F. DeGrado, et al. (2006)
J. Biol. Chem. 281, 36732-36741
   Abstract »    Full Text »    PDF »
Talin1 Regulates TCR-Mediated LFA-1 Function.
W. T. N. Simonson, S. J. Franco, and A. Huttenlocher (2006)
J. Immunol. 177, 7707-7714
   Abstract »    Full Text »    PDF »
{alpha}-Chain phosphorylation of the human leukocyte CD11b/CD18 (Mac-1) integrin is pivotal for integrin activation to bind ICAMs and leukocyte extravasation.
S. C. Fagerholm, M. Varis, M. Stefanidakis, T. J. Hilden, and C. G. Gahmberg (2006)
Blood 108, 3379-3386
   Abstract »    Full Text »    PDF »
How the headpiece hinge angle is opened: new insights into the dynamics of integrin activation.
E. Puklin-Faucher, M. Gao, K. Schulten, and V. Vogel (2006)
J. Cell Biol. 175, 349-360
   Abstract »    Full Text »    PDF »
AL-57, a ligand-mimetic antibody to integrin LFA-1, reveals chemokine-induced affinity up-regulation in lymphocytes.
M. Shimaoka, M. Kim, E. H. Cohen, W. Yang, N. Astrof, D. Peer, A. Salas, A. Ferrand, and T. A. Springer (2006)
PNAS 103, 13991-13996
   Abstract »    Full Text »    PDF »
Regulation of outside-in signaling and affinity by the beta2 I domain of integrin {alpha}Lbeta2.
J. Chen, W. Yang, M. Kim, C. V. Carman, and T. A. Springer (2006)
PNAS 103, 13062-13067
   Abstract »    Full Text »    PDF »
Occupation of {alpha}vbeta3-integrin by endogenous ligands modulates IGF-I receptor activation and proliferation of human intestinal smooth muscle.
J. F. Kuemmerle (2006)
Am J Physiol Gastrointest Liver Physiol 290, G1194-G1202
   Abstract »    Full Text »    PDF »
Shedding of lymphocyte function-associated antigen-1 (LFA-1) in a human inflammatory response.
B. J. Evans, A. McDowall, P. C. Taylor, N. Hogg, D. O. Haskard, and R. C. Landis (2006)
Blood 107, 3593-3599
   Abstract »    Full Text »    PDF »
Transition from Rolling to Firm Adhesion Can Be Mimicked by Extension of Integrin {alpha}Lbeta2 in an Intermediate Affinity State.
A. Salas, M. Shimaoka, U. Phan, M. Kim, and T. A. Springer (2006)
J. Biol. Chem. 281, 10876-10882
   Abstract »    Full Text »    PDF »
Non-cytotoxic Cobra Cardiotoxin A5 Binds to {alpha}vbeta3 Integrin and Inhibits Bone Resorption: IDENTIFICATION OF CARDIOTOXINS AS NON-RGD INTEGRIN-BINDING PROTEINS OF THE Ly-6 FAMILY.
P.-L. Wu, S.-C. Lee, C.-C. Chuang, S. Mori, N. Akakura, W.-g. Wu, and Y. Takada (2006)
J. Biol. Chem. 281, 7937-7945
   Abstract »    Full Text »    PDF »
The Activity of the Vinculin Binding Sites in Talin Is Influenced by the Stability of the Helical Bundles That Make Up The Talin Rod.
B. Patel, A. R. Gingras, A. A. Bobkov, L. M. Fujimoto, M. Zhang, R. C. Liddington, D. Mazzeo, J. Emsley, G. C. K. Roberts, I. L. Barsukov, et al. (2006)
J. Biol. Chem. 281, 7458-7467
   Abstract »    Full Text »    PDF »
Dynamic shifts in LFA-1 affinity regulate neutrophil rolling, arrest, and transmigration on inflamed endothelium.
C. E. Green, U. Y. Schaff, M. R. Sarantos, A. F. H. Lum, D. E. Staunton, and S. I. Simon (2006)
Blood 107, 2101-2111
   Abstract »    Full Text »    PDF »
Rational Design of Intercellular Adhesion Molecule-1 (ICAM-1) Variants for Antagonizing Integrin Lymphocyte Function-associated Antigen-1-dependent Adhesion.
G. Song, G. A. Lazar, T. Kortemme, M. Shimaoka, J. R. Desjarlais, D. Baker, and T. A. Springer (2006)
J. Biol. Chem. 281, 5042-5049
   Abstract »    Full Text »    PDF »
Leukocyte Recruitment and Vascular Injury in Diabetic Nephropathy.
E. Galkina and K. Ley (2006)
J. Am. Soc. Nephrol. 17, 368-377
   Abstract »    Full Text »    PDF »
Alterations in blood-brain barrier ICAM-1 expression and brain microglial activation after {lambda}-carrageenan-induced inflammatory pain.
J. D. Huber, C. R. Campos, K. S. Mark, and T. P. Davis (2006)
Am J Physiol Heart Circ Physiol 290, H732-H740
   Abstract »    Full Text »    PDF »
Imaging Signal Transduction in Living Cells with Fluorescent Proteins.
M. R. Philips (2005)
Sci. STKE 2005, tr28
   Abstract »    Full Text »    PDF »
Specific integrin {alpha} and {beta} chain phosphorylations regulate LFA-1 activation through affinity-dependent and -independent mechanisms.
S. C. Fagerholm, T. J. Hilden, S. M. Nurmi, and C. G. Gahmberg (2005)
J. Cell Biol. 171, 705-715
   Abstract »    Full Text »    PDF »
Fundamentally different roles for LFA-1, Mac-1 and {alpha}4-integrin in neutrophil chemotaxis.
B. Heit, P. Colarusso, and P. Kubes (2005)
J. Cell Sci. 118, 5205-5220
   Abstract »    Full Text »    PDF »
LFA-1 Is a Key Determinant for Preferential Infection of Memory CD4+ T Cells by Human Immunodeficiency Virus Type 1.
M. R. Tardif and M. J. Tremblay (2005)
J. Virol. 79, 13714-13724
   Abstract »    Full Text »    PDF »
Talin phosphorylation sites mapped by mass spectrometry.
B. Ratnikov, C. Ptak, J. Han, J. Shabanowitz, D. F. Hunt, and M. H. Ginsberg (2005)
J. Cell Sci. 118, 4921-4923
   Full Text »    PDF »
Tec Kinases Regulate TCR-Mediated Recruitment of Signaling Molecules and Integrin-Dependent Cell Adhesion.
L. D. Finkelstein, Y. Shimizu, and P. L. Schwartzberg (2005)
J. Immunol. 175, 5923-5930
   Abstract »    Full Text »    PDF »
The {alpha}v{beta}6 integrin receptor for Foot-and-mouth disease virus is expressed constitutively on the epithelial cells targeted in cattle.
P. Monaghan, S. Gold, J. Simpson, Z. Zhang, P. H. Weinreb, S. M. Violette, S. Alexandersen, and T. Jackson (2005)
J. Gen. Virol. 86, 2769-2780
   Abstract »    Full Text »    PDF »
Specification of the Direction of Adhesive Signaling by the Integrin {beta} Cytoplasmic Domain.
E. G. Arias-Salgado, S. Lizano, S. J. Shattil, and M. H. Ginsberg (2005)
J. Biol. Chem. 280, 29699-29707
   Abstract »    Full Text »    PDF »
Structural Dynamics of {alpha}-Actinin-Vinculin Interactions.
P. R. J. Bois, R. A. Borgon, C. Vonrhein, and T. Izard (2005)
Mol. Cell. Biol. 25, 6112-6122
   Abstract »    Full Text »    PDF »
Regulation of LFA-1 Activity through Cytoskeleton Remodeling and Signaling Components Modulates the Efficiency of HIV Type-1 Entry in Activated CD4+ T Lymphocytes.
M. R. Tardif and M. J. Tremblay (2005)
J. Immunol. 175, 926-935
   Abstract »    Full Text »    PDF »
A talin-dependent LFA-1 focal zone is formed by rapidly migrating T lymphocytes.
A. Smith, Y. R. Carrasco, P. Stanley, N. Kieffer, F. D. Batista, and N. Hogg (2005)
J. Cell Biol. 170, 141-151
   Abstract »    Full Text »    PDF »
Membrane-proximal {alpha}/{beta} Stalk Interactions Differentially Regulate Integrin Activation.
T. Kamata, M. Handa, Y. Sato, Y. Ikeda, and S. Aiso (2005)
J. Biol. Chem. 280, 24775-24783
   Abstract »    Full Text »    PDF »
Vav1 and Rac Control Chemokine-promoted T Lymphocyte Adhesion Mediated by the Integrin {alpha}4{beta}1.
D. Garcia-Bernal, N. Wright, E. Sotillo-Mallo, C. Nombela-Arrieta, J. V. Stein, X. R. Bustelo, and J. Teixido (2005)
Mol. Biol. Cell 16, 3223-3235
   Abstract »    Full Text »    PDF »
Importance of integrin LFA-1 deactivation for the generation of immune responses.
M. Semmrich, A. Smith, C. Feterowski, S. Beer, B. Engelhardt, D. H. Busch, B. Bartsch, M. Laschinger, N. Hogg, K. Pfeffer, et al. (2005)
J. Exp. Med. 201, 1987-1998
   Abstract »    Full Text »    PDF »
Intracellular Trafficking of CD23: Differential Regulation in Humans and Mice by Both Extracellular and Intracellular Exons.
G. Montagnac, A. Molla-Herman, J. Bouchet, L. C. H. Yu, D. H. Conrad, M. H. Perdue, and A. Benmerah (2005)
J. Immunol. 174, 5562-5572
   Abstract »    Full Text »    PDF »
Disrupting integrin transmembrane domain heterodimerization increases ligand binding affinity, not valency or clustering.
B.-H. Luo, C. V. Carman, J. Takagi, and T. A. Springer (2005)
PNAS 102, 3679-3684
   Abstract »    Full Text »    PDF »
Transmembrane Domain Helix Packing Stabilizes Integrin {alpha}IIb{beta}3 in the Low Affinity State.
A. W. Partridge, S. Liu, S. Kim, J. U. Bowie, and M. H. Ginsberg (2005)
J. Biol. Chem. 280, 7294-7300
   Abstract »    Full Text »    PDF »
A push-pull mechanism for regulating integrin function.
W. Li, D. G. Metcalf, R. Gorelik, R. Li, N. Mitra, V. Nanda, P. B. Law, J. D. Lear, W. F. DeGrado, and J. S. Bennett (2005)
PNAS 102, 1424-1429
   Abstract »    Full Text »    PDF »
A specific {alpha}5{beta}1-integrin conformation promotes directional integrin translocation and fibronectin matrix formation.
K. Clark, R. Pankov, M. A. Travis, J. A. Askari, A. P. Mould, S. E. Craig, P. Newham, K. M. Yamada, and M. J. Humphries (2005)
J. Cell Sci. 118, 291-300
   Abstract »    Full Text »    PDF »
{alpha}L-Integrin I domain cyclic peptide antagonist selectively inhibits T cell adhesion to pancreatic islet microvascular endothelium.
M. Huang, K. Matthews, T. J. Siahaan, and C. G. Kevil (2005)
Am J Physiol Gastrointest Liver Physiol 288, G67-G73
   Abstract »    Full Text »    PDF »
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 {alpha}4{beta}7.
J. Chen, J. Takagi, C. Xie, T. Xiao, B.-H. Luo, and T. A. Springer (2004)
J. Biol. Chem. 279, 55556-55561
   Abstract »    Full Text »    PDF »
A 50-A Separation of the Integrin {alpha}v{beta}3 Extracellular Domain C Termini Reveals an Intermediate Activation State.
S. E. Gline, S. Cambier, C. Govaerts, and S. L. Nishimura (2004)
J. Biol. Chem. 279, 54567-54572
   Abstract »    Full Text »    PDF »
The primacy of affinity over clustering in regulation of adhesiveness of the integrin {alpha}L{beta}2.
M. Kim, C. V. Carman, W. Yang, A. Salas, and T. A. Springer (2004)
J. Cell Biol. 167, 1241-1253
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)