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Functional atlas of the integrin adhesome
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A new approach in the study of molecular basis of integrin-mediated signaling which is based on detailed data mining of published experimental studies. It provides a visual perspective of the entire integrin signaling network known so far. Further insights are provided through simulations detecting common network motifs.
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Zaidel-Bar R., Itzkovitz S., Ma'ayan A., Iyengar R., and Geiger B. Functional atlas of the integrin adhesome. Nat Cell Biol 9 (2007) 858-867. A new approach in the study of molecular basis of integrin-mediated signaling which is based on detailed data mining of published experimental studies. It provides a visual perspective of the entire integrin signaling network known so far. Further insights are provided through simulations detecting common network motifs.
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Zaidel-Bar, R.1
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A mechanosensory complex that mediates the endothelial cell response to fluid shear stress
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Tzima E., Irani-Tehrani M., Kiosses W.B., Dejana E., Schultz D.A., Engelhardt B., Cao G.Y., DeLisser H., and Schwartz M.A. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature 437 (2005) 426-431
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An outstanding work on visualization and analysis of the role of focal adhesions in force transduction during cell migration. This study showed small nascent adhesions near the leading edge that are more important for the transmission of strong propulsive tractions than large, mature focal adhesions. They showed that mature focal adhesions act as passive anchorage points responsible for maintaining a spread cell morphology.
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Beningo K.A., Dembo M., Kaverina I., Small J.V., and Wang Y.L. Nascent focal adhesions are responsible for the generation of strong propulsive forces in migrating fibroblasts. J Cell Biol 153 (2001) 881-888. An outstanding work on visualization and analysis of the role of focal adhesions in force transduction during cell migration. This study showed small nascent adhesions near the leading edge that are more important for the transmission of strong propulsive tractions than large, mature focal adhesions. They showed that mature focal adhesions act as passive anchorage points responsible for maintaining a spread cell morphology.
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From the cover: cells lying on a bed of microneedles: an approach to isolate mechanical force
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Tan J.L., Tien J., Pirone D.M., Gray D.S., Bhadriraju K., and Chen C.S. From the cover: cells lying on a bed of microneedles: an approach to isolate mechanical force. PNAS 100 (2003) 1484-1489
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High resolution traction force microscopy based on experimental and computational advances
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A thorough discussion of the latest improvements in experimental and computational techniques used in high-resolution traction force microscopy. Strength and limitations of established and newly developed procedures for the reconstruction of cellular traction force on flat elastic substrate are thoroughly discussed.
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Sabass B., Gardel M.L., Waterman C.M., and Schwarz U.S. High resolution traction force microscopy based on experimental and computational advances. Biophys J 94 (2008) 207-220. A thorough discussion of the latest improvements in experimental and computational techniques used in high-resolution traction force microscopy. Strength and limitations of established and newly developed procedures for the reconstruction of cellular traction force on flat elastic substrate are thoroughly discussed.
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Sabass, B.1
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Probing intracellular force distributions by high-resolution live cell imaging and inverse dynamics
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Ji L., Loerke D., Gardel M., and Danuser G. Probing intracellular force distributions by high-resolution live cell imaging and inverse dynamics. Methods in Cell Biology vol 83 (2007), Academic Press 200-237
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Methods in Cell Biology
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Ji, L.1
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Quantitative fluorescent speckle microscopy of cytoskeleton dynamics
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Danuser G., and Waterman-Storer C.M. Quantitative fluorescent speckle microscopy of cytoskeleton dynamics. Annu Rev Biophys Biomol Struct 35 (2006) 361-387
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Differential transmission of actin motion within focal adhesions
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Hu K., Ji L., Applegate K., Danuser G., and Waterman-Storer C.M. Differential transmission of actin motion within focal adhesions. Science 315 (2007) 111-115
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Spatiotemporal image correlation spectroscopy (STICS) theory, verification, and application to protein velocity mapping in living CHO cells
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Hebert B., Costantino S., and Wiseman P.W. Spatiotemporal image correlation spectroscopy (STICS) theory, verification, and application to protein velocity mapping in living CHO cells. Biophys J 88 (2005) 3601-3614
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Maiti S., Haupts U., and Webb W.W. Fluorescence correlation spectroscopy: diagnostics for sparse molecules. Proc Natl Acad Sci U S A 94 (1997) 11753-11757
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Probing the integrin-actin linkage using high-resolution protein velocity mapping
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Shattil S.J. Integrins and Src: dynamic duo of adhesion signaling. Trends Cell Biol 15 (2005) 399-403
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Shedding light on cell signaling: interpretation of FRET biosensors
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This is a concise yet authoritative review of recent advances in the detection and interpretation of spatiotemporal activities of intact proteins in live cells using biosensors.
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Gaits F., and Hahn K. Shedding light on cell signaling: interpretation of FRET biosensors. Sci STKE 2003 (2003) PE3. This is a concise yet authoritative review of recent advances in the detection and interpretation of spatiotemporal activities of intact proteins in live cells using biosensors.
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Sci STKE
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Gaits, F.1
Hahn, K.2
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Phosphatidylinositol 3-kinase-dependent membrane association of the Bruton's tyrosine kinase pleckstrin homology domain visualized in single living cells
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Varnai P., Rother K.I., and Balla T. Phosphatidylinositol 3-kinase-dependent membrane association of the Bruton's tyrosine kinase pleckstrin homology domain visualized in single living cells. J Biol Chem 274 (1999) 10983-10989
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Targeting of Golgi-specific pleckstrin homology domains involves both PtdIns 4-kinase-dependent and -independent components
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20
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Receptor-induced transient reduction in plasma membrane PtdIns(4,5)P2 concentration monitored in living cells
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In this paper, translocation of a domain that binds to the activated form of the target protein is used as a robust and simple readout of protein activity.
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Stauffer T.P., Ahn S., and Meyer T. Receptor-induced transient reduction in plasma membrane PtdIns(4,5)P2 concentration monitored in living cells. Curr Biol 8 (1998) 343-346. In this paper, translocation of a domain that binds to the activated form of the target protein is used as a robust and simple readout of protein activity.
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Curr Biol
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Stauffer, T.P.1
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3H]inositol-labeled phosphoinositide pools. J Cell Biol 143 (1998) 501-510
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Burd C.G., and Emr S.D. Phosphatidylinositol(3)-phosphate signaling mediated by specific binding to RING FYVE domains. Mol Cell 2 (1998) 157-162
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The pleckstrin homology domains of protein kinase B and GRP1 (general receptor for phosphoinositides-1) are sensitive and selective probes for the cellular detection of phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 3,4,5-trisphosphate in vivo
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Gray A., Van Der Kaay J., and Downes C.P. The pleckstrin homology domains of protein kinase B and GRP1 (general receptor for phosphoinositides-1) are sensitive and selective probes for the cellular detection of phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 3,4,5-trisphosphate in vivo. Biochem J 344 Pt 3 (1999) 929-936
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0034644603
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Localized Rac activation dynamics visualized in living cells
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••]. This paper describes the prototype FRET biosensor for GTPase activity, showing that FRET between a GTPase protein and a fragment of a downstream effector could be used to study GTPase nucleotide state in living cells. The paper revealed gradients of Rac activity controlling cell polarization.
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••]. This paper describes the prototype FRET biosensor for GTPase activity, showing that FRET between a GTPase protein and a fragment of a downstream effector could be used to study GTPase nucleotide state in living cells. The paper revealed gradients of Rac activity controlling cell polarization.
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Science
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Kraynov, V.S.1
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Hahn, K.M.6
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25
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0033605542
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Imaging protein kinase Calpha activation in cells
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Ng T., Squire A., Hansra G., Bornancin F., Prevostel C., Hanby A., Harris W., Barnes D., Schmidt S., Mellor H., et al. Imaging protein kinase Calpha activation in cells. Science 283 (1999) 2085-2089
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Schmidt, S.9
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26
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A genetically engineered, protein-based optical biosensor of myosin II regulatory light chain phosphorylation
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One of the first biosensors demonstrating that cytoskeletal protein conformation, rather than simple localization, could be visualized in living cells. This paper supported models of polarized cell movement and the role of myosin activity.
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Post P.L., Trybus K.M., and Taylor D.L. A genetically engineered, protein-based optical biosensor of myosin II regulatory light chain phosphorylation. J Biol Chem 269 (1994) 12880-12887. One of the first biosensors demonstrating that cytoskeletal protein conformation, rather than simple localization, could be visualized in living cells. This paper supported models of polarized cell movement and the role of myosin activity.
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Post, P.L.1
Trybus, K.M.2
Taylor, D.L.3
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27
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4644266043
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Activation of endogenous Cdc42 visualized in living cells
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This biosensor demonstrated that activation of endogenous Cdc42 could be studied in living cells using bright dyes. A fragment of the Cdc42 effector WASP was derivatized with a dye whose fluorescence changed upon binding to the Cdc42 target. The use of a fluorescent dye provides enhanced signal and the ability to image multiple activities at different wavelengths, but till date requires injection of the biosensor.
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Nalbant P., Hodgson L., Kraynov V., Toutchkine A., and Hahn K.M. Activation of endogenous Cdc42 visualized in living cells. Science 305 (2004) 1615-1619. This biosensor demonstrated that activation of endogenous Cdc42 could be studied in living cells using bright dyes. A fragment of the Cdc42 effector WASP was derivatized with a dye whose fluorescence changed upon binding to the Cdc42 target. The use of a fluorescent dye provides enhanced signal and the ability to image multiple activities at different wavelengths, but till date requires injection of the biosensor.
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Science
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Nalbant, P.1
Hodgson, L.2
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Toutchkine, A.4
Hahn, K.M.5
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28
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Spatio-temporal images of growth-factor-induced activation of Ras and Rap1
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Here the advent of fluorescent proteins undergoing FRET permitted the construction of a GTPase biosensor that was completely genetically encoded. Linking all components in a single chain produced a biosensor that was free of many of the image processing corrections required for intermolecular FRET.
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Mochizuki N., Yamashita S., Kurokawa K., Ohba Y., Nagai T., Miyawaki A., and Matsuda M. Spatio-temporal images of growth-factor-induced activation of Ras and Rap1. Nature 411 (2001) 1065-1068. Here the advent of fluorescent proteins undergoing FRET permitted the construction of a GTPase biosensor that was completely genetically encoded. Linking all components in a single chain produced a biosensor that was free of many of the image processing corrections required for intermolecular FRET.
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Nature
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Mochizuki, N.1
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Miyawaki, A.6
Matsuda, M.7
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29
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Spatiotemporal dynamics of RhoA activity in migrating cells
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This paper describes a RhoA biosensor in which the genetically encoded FRET pair was moved to the inside of the biosensor chain, leaving the C terminus free for normal interaction with GDI. GDI is an important regulator of RhoA membrane localization. This paper revealed substantial RhoA activation at the leading edge of motile cells.
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Pertz O., Hodgson L., Klemke R.L., and Hahn K.M. Spatiotemporal dynamics of RhoA activity in migrating cells. Nature 440 (2006) 1069-1072. This paper describes a RhoA biosensor in which the genetically encoded FRET pair was moved to the inside of the biosensor chain, leaving the C terminus free for normal interaction with GDI. GDI is an important regulator of RhoA membrane localization. This paper revealed substantial RhoA activation at the leading edge of motile cells.
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Nature
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Pertz, O.1
Hodgson, L.2
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Violin J.D., Zhang J., Tsien R.Y., and Newton A.C. A genetically encoded fluorescent reporter reveals oscillatory phosphorylation by protein kinase C. J Cell Biol 161 (2003) 899-909
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J Cell Biol
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Genetically encoded fluorescent reporters of protein tyrosine kinase activities in living cells
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••] demonstrated a broadly applicable biosensor design, reporting modification of enzyme substrates.
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••] demonstrated a broadly applicable biosensor design, reporting modification of enzyme substrates.
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Proc Natl Acad Sci U S A
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Adhesion-dependent cell mechanosensitivity
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A comprehensive review of cellular mechanosensitivity.
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Bershadsky A.D., Balaban N.Q., and Geiger B. Adhesion-dependent cell mechanosensitivity. Annu Rev Cell Dev Biol 19 (2003) 677-695. A comprehensive review of cellular mechanosensitivity.
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Bershadsky, A.D.1
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Local force and geometry sensing regulate cell functions
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An insightful review of cell responses to local force and rigidity sensing.
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Vogel V., and Sheetz M. Local force and geometry sensing regulate cell functions. Nat Rev Mol Cell Biol 7 (2006) 265-275. An insightful review of cell responses to local force and rigidity sensing.
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Vogel, V.1
Sheetz, M.2
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34
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17844388845
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Visualizing the mechanical activation of Src
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Src regulates integrin-cytoskeleton interaction. By applying external mechanical stimulation localized at adhesion sites and using a FRET biosensor this study showed a rapid Src activation at stimulation sites followed by a wave of Src activation that propagates along the plasma membrane. The force-induced directional and long-range Src activation wave is destroyed by the disruption of actin network or microtubules indicating the role of cytoskeleton on force-induced Src activation.
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Wang Y., Botvinick E.L., Zhao Y., Berns M.W., Usami S., Tsien R.Y., and Chien S. Visualizing the mechanical activation of Src. Nature 434 (2005) 1040-1045. Src regulates integrin-cytoskeleton interaction. By applying external mechanical stimulation localized at adhesion sites and using a FRET biosensor this study showed a rapid Src activation at stimulation sites followed by a wave of Src activation that propagates along the plasma membrane. The force-induced directional and long-range Src activation wave is destroyed by the disruption of actin network or microtubules indicating the role of cytoskeleton on force-induced Src activation.
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Nature
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Wang, Y.1
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Galbraith C.G., Yamada K.M., and Sheetz M.P. The relationship between force and focal complex development. J Cell Biol 159 (2002) 695-705
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Integrins regulate GTP-Rac localized effector interactions through dissociation of Rho-GDI
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del Pozo M.A., Kiosses W.B., Alderson N.B., Meller N., Hahn K.M., and Schwartz M.A. Integrins regulate GTP-Rac localized effector interactions through dissociation of Rho-GDI. Nat Cell Biol 4 (2002) 232-239
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Nat Cell Biol
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37
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37549060016
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Spatial and temporal regulation of focal adhesion kinase activity in living cells
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In this work the relationship between the maturation of an initial adhesion into a focal complex and its ability to exert migration force was probed by the application of mechanical force to fibronectin receptors from inside and outside the cell. This study showed that cells use mechanical force as a signal to strengthen initial adhesion complexes into focal complexes and regulate the amount of traction force applied to adhesion sites localized in different regions of lamella.
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Cai X., Lietha D., Ceccarelli D.F., Karginov A.V., Rajfur Z., Jacobson K., Hahn K.M., Eck M.J., and Schaller M.D. Spatial and temporal regulation of focal adhesion kinase activity in living cells. Mol Cell Biol 28 (2008) 201-214. In this work the relationship between the maturation of an initial adhesion into a focal complex and its ability to exert migration force was probed by the application of mechanical force to fibronectin receptors from inside and outside the cell. This study showed that cells use mechanical force as a signal to strengthen initial adhesion complexes into focal complexes and regulate the amount of traction force applied to adhesion sites localized in different regions of lamella.
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Mol Cell Biol
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Cai, X.1
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38
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Conformational changes in human integrin alphaIIbbeta3 after platelet activation, monitored by FRET
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Coutinho A., Garcia C., Gonzalez-Rodriguez J., and Lillo M.P. Conformational changes in human integrin alphaIIbbeta3 after platelet activation, monitored by FRET. Biophys Chem 130 (2007) 76-87
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Visual snapshots of intracellular kinase activity at the onset of mitosis
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Dai Z., Dulyaninova N.G., Kumar S., Bresnick A.R., and Lawrence D.S. Visual snapshots of intracellular kinase activity at the onset of mitosis. Chem Biol 14 (2007) 1254-1260
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40
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A biosensor of S100A4 metastasis factor activation: inhibitor screening and cellular activation dynamics
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Garrett S.C., Hodgson L., Rybin A., Toutchkine A., Hahn K.M., Lawrence D.S., and Bresnick A.R. A biosensor of S100A4 metastasis factor activation: inhibitor screening and cellular activation dynamics. Biochemistry 47 (2008) 986-996
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Biochemistry
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A fluorescence resonance energy transfer activation sensor for Arf6
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Hall B., McLean M.A., Davis K., Casanova J.E., Sligar S.G., and Schwartz M.A. A fluorescence resonance energy transfer activation sensor for Arf6. Anal Biochem 374 (2008) 243-249
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42
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