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A structural mechanism of integrin α(IIb)β(3) 'inside-out' activation as regulated by its cytoplasmic face
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3 reveals low-affinity interactions between the α and β subunit tails that are perturbed by activating mutations and also upon binding by the talin head domain, thus providing a structural basis for integrin activation.
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3 reveals low-affinity interactions between the α and β subunit tails that are perturbed by activating mutations and also upon binding by the talin head domain, thus providing a structural basis for integrin activation.
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Alvarez et al. perform X-ray crystallography of the integrin-binding and activating fragment of talin and suggest a two-step mechanism for talin-based integrin activation.
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Garcia-Alvarez B., de Pereda J.M., Calderwood D.A., Ulmer T.S., Critchley D., Campbell I.D., Ginsberg M.H., Liddington R.C. Structural determinants of integrin recognition by talin. Mol. Cell. 11:2003;49-58 Alvarez et al. perform X-ray crystallography of the integrin-binding and activating fragment of talin and suggest a two-step mechanism for talin-based integrin activation.
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The phosphotyrosine binding-like domain of talin activates integrins
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This structural study shows that the F3 subdomain, a PTB-resembling subdomain in the talin head, binds to the NPX(Y/F) motif in the integrin cytoplasmic tails and that overexpression of this domain in cells leads to integrin activation.
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Calderwood D.A., Yan B., de Pereda J.M., Alvarez B.G., Fujioka Y., Liddington R.C., Ginsberg M.H. The phosphotyrosine binding-like domain of talin activates integrins. J. Biol. Chem. 277:2002;21749-21758 This structural study shows that the F3 subdomain, a PTB-resembling subdomain in the talin head, binds to the NPX(Y/F) motif in the integrin cytoplasmic tails and that overexpression of this domain in cells leads to integrin activation.
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3 and assay for integrin activation in a low-talin background. They establish that talin directly affects integrin affinity and is the major activator of integrins irrespective of the nature of the signaling pathway involved.
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3 and assay for integrin activation in a low-talin background. They establish that talin directly affects integrin affinity and is the major activator of integrins irrespective of the nature of the signaling pathway involved.
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α-Actinin and vinculin are PIP2-binding proteins involved in signaling by tyrosine kinase
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The interaction of the cell-contact proteins VASP and vinculin is regulated by phosphatidylinositol-4,5-bisphosphate
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Martel V., Racaud-Sultan C., Dupe S., Marie C., Paulhe F., Galmiche A., Block M.R., Albiges-Rizo C. Conformation, localization and integrin binding of talin depend on its interaction with phosphoinositides. J. Biol. Chem. 276:2001;21217-21227.
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Talin loss-of-function uncovers roles in cell contractility and migration in C. elegans
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In this recent paper, the authors report the RNAi-generated loss-of-function phenotype in C. elegans. Talin knockdown in these cells leads to migratory and cytoskeletal defects, with the phenotype closely resembling the integrin-knockdown phenotype, which suggests a role for talin in the regulation of integrin signals.
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Cram E.J., Clark S.G., Schwarzbauer J.E. Talin loss-of-function uncovers roles in cell contractility and migration in C. elegans. J. Cell Sci. 116:2003;3871-3878 In this recent paper, the authors report the RNAi-generated loss-of-function phenotype in C. elegans. Talin knockdown in these cells leads to migratory and cytoskeletal defects, with the phenotype closely resembling the integrin-knockdown phenotype, which suggests a role for talin in the regulation of integrin signals.
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Cram, E.J.1
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Talin is essential for integrin function in Drosophila
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In this paper, the authors identify the Drosophila gene that encodes talin and show that mutations in this gene lead to a phenotype similar to the loss of integrins. Also, they show that the key role of talin is to juxtapose integrins with actin and is not required for integrin localization to the cell surface.
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Brown N.H., Gregory S.L., Rickoll W.L., Fessler L.I., Prout M., White R.A., Fristrom J.W. Talin is essential for integrin function in Drosophila. Dev. Cell. 3:2002;569-579 In this paper, the authors identify the Drosophila gene that encodes talin and show that mutations in this gene lead to a phenotype similar to the loss of integrins. Also, they show that the key role of talin is to juxtapose integrins with actin and is not required for integrin localization to the cell surface.
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Brown, N.H.1
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Disruption of the talin gene arrests mouse development at the gastrulation stage
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Monkley S.J., Zhou X.H., Kinston S.J., Giblett S.M., Hemmings L., Priddle H., Brown J.E., Pritchard C.A., Critchley D.R., Fassler R. Disruption of the talin gene arrests mouse development at the gastrulation stage. Dev. Dyn. 219:2000;560-574.
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0041461882
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Two-piconewton slip bond between fibronectin and the cytoskeleton depends on talin
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Jiang et al. employ laser tweezer microscopy to estimate the forces required for reinforcing extracellular-matrix-integrin-actin cytoskeletal linkages. Lack of these forces in talin-null cells and in actin-binding- deficient talin mutants implicates talin as being essential for the reinforcement of these linkages.
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Jiang G., Giannone G., Critchley D.R., Fukumoto E., Sheetz M.P. Two-piconewton slip bond between fibronectin and the cytoskeleton depends on talin. Nature. 424:2003;334-337 Jiang et al. employ laser tweezer microscopy to estimate the forces required for reinforcing extracellular-matrix-integrin- actin cytoskeletal linkages. Lack of these forces in talin-null cells and in actin-binding-deficient talin mutants implicates talin as being essential for the reinforcement of these linkages.
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Jiang, G.1
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28
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0037038412
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Type Iγ phosphatidylinositol phosphate kinase targets and regulates focal adhesions
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This pioneering report demonstrates the talin-mediated recruitment of the PIP2-synthesizing enzyme PIPKIγ661 to adhesions. PIPKIγ 661affects talin localization and is stimulated by FAK, thereby implicating it in the regulation of adhesion dynamics.
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Ling K., Doughman R.L., Firestone A.J., Bunce M.W., Anderson R.A. Type Iγ phosphatidylinositol phosphate kinase targets and regulates focal adhesions. Nature. 420:2002;89-93 This pioneering report demonstrates the talin-mediated recruitment of the PIP2-synthesizing enzyme PIPKIγ661 to adhesions. PIPKIγ661affects talin localization and is stimulated by FAK, thereby implicating it in the regulation of adhesion dynamics.
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Nature
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Ling, K.1
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Recruitment and regulation of phosphatidylinositol phosphate kinase type 1γ by the FERM domain of talin
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This paper corroborates the evidence for talin-mediated recruitment of a brain splice variant of PIPKIγ to synapses and also to focal adhesion plaques in non-neuronal cells.
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Di Paolo G., Pellegrini L., Letinic K., Cestra G., Zoncu R., Voronov S., Chang S., Guo J., Wenk M.R., De Camilli P. Recruitment and regulation of phosphatidylinositol phosphate kinase type 1γ by the FERM domain of talin. Nature. 420:2002;85-89 This paper corroborates the evidence for talin-mediated recruitment of a brain splice variant of PIPKIγ to synapses and also to focal adhesion plaques in non-neuronal cells.
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Nature
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Di Paolo, G.1
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Recruitment of the Arp2/3 complex to vinculin: Coupling membrane protrusion to matrix adhesion
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This breakthrough investigation provides novel evidence for a direct and transient interaction between vinculin and the Arp2/3 complex in early adhesions, suggesting a link between adhesion formation and protrusion dynamics.
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DeMali K.A., Barlow C.A., Burridge K. Recruitment of the Arp2/3 complex to vinculin: coupling membrane protrusion to matrix adhesion. J. Cell Biol. 159:2002;881-891 This breakthrough investigation provides novel evidence for a direct and transient interaction between vinculin and the Arp2/3 complex in early adhesions, suggesting a link between adhesion formation and protrusion dynamics.
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Yan B., Calderwood D.A., Yaspan B., Ginsberg M.H. Calpain cleavage promotes talin binding to the β3 integrin cytoplasmic domain. J. Biol. Chem. 276:2001;28164-28170.
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Peptide-specific antibodies localize the major lipid binding sites of talin dimers to oppositely arranged N-terminal 47 kDa subdomains
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Layilin, a novel talin-binding transmembrane protein homologous with C-type lectins, is localized in membrane ruffles
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Megakaryocytes derived from embryonic stem cells implicate CalDAG-GEFI in integrin signaling
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Eto K., Murphy R., Kerrigan S.W., Bertoni A., Stuhlmann H., Nakano T., Leavitt A.D., Shattil S.J. Megakaryocytes derived from embryonic stem cells implicate CalDAG-GEFI in integrin signaling. Proc. Natl. Acad. Sci. U.S.A. 99:2002;12819-12824.
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