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This paper investigates how cell adhesion is altered as matrix remodeling progresses in three dimensions. They find that as fibroblasts encounter resistance in a collagen matrix, and their overall morphology changes from dendritic to bipolar, cell-matrix adhesions change from punctate to focal adhesions. Rho kinase activity is needed for these changes to occur.
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Tamariz E., Grinnell F. Modulation of fibroblast morphology and adhesion during collagen matrix remodeling. Mol Biol Cell. 13:2002;3915-3929 This paper investigates how cell adhesion is altered as matrix remodeling progresses in three dimensions. They find that as fibroblasts encounter resistance in a collagen matrix, and their overall morphology changes from dendritic to bipolar, cell-matrix adhesions change from punctate to focal adhesions. Rho kinase activity is needed for these changes to occur.
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Moores S.L., Selfors L.M., Fredericks J., Breit T., Fujikawa K., Alt F.W., Brugge J.S., Swat W. Vav family proteins couple to diverse cell surface receptors. Mol Cell Biol. 20:2000;6364-6373.
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Hasegawa H., Kiyokawa E., Tanaka S., Nagashima K., Gotoh N., Shibuya M., Kurata T., Matsuda M. DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane. Mol Cell Biol. 16:1996;1770-1776.
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••], identify Dock180, a protein lacking a conventional Dbl homology/Pleckstrin homology tandem domain, as an activator of Rac. Evidence is presented that Dock180 binds ELMO and stimulates the GTP-loading of Rac.
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••], identify Dock180, a protein lacking a conventional Dbl homology/Pleckstrin homology tandem domain, as an activator of Rac. Evidence is presented that Dock180 binds ELMO and stimulates the GTP-loading of Rac.
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Brugnera, E.1
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••], they present evidence that DOCK180 exchange activity on Rac does not require the presence of ELMO.
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Del Pozo and colleagues present a novel mechanism for the spatial control of Rac signaling in response to integrin adhesion. They provide evidence that integrin engagement initiates translocation of cytoplasmic GTP-bound Rac to the plasma membrane by RhoGDI. At the membrane, RacGTP is released from RhoGDI and is free to interact with effectors.
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Del Pozo M.A., Kiosses W.B., Alderson N.B., Meller N., Hahn K.M., Schwartz M.A. Integrins regulate GTP-Rac localized effector interactions through dissociation of RhoGDI. Nat Cell Biol. 4:2002;232-239 Del Pozo and colleagues present a novel mechanism for the spatial control of Rac signaling in response to integrin adhesion. They provide evidence that integrin engagement initiates translocation of cytoplasmic GTP-bound Rac to the plasma membrane by RhoGDI. At the membrane, RacGTP is released from RhoGDI and is free to interact with effectors.
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The experiments in this paper suggest that paxillin is involved in the transient decrease in Rho activity following integrin engagement. Evidence is provided that integrin-mediated tyrosine phosphorylation of paxillin generates a binding site for p120RasGAP, thereby liberating it from association with p190RhoGAP. p190RhoGAP freed from p120RasGAP is activated and contributes to the decrease in RhoA activity.
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Saoncella S., Echtermeyer F., Denhez F., Nowlen J.K., Mosher D.F., Robinson S.D., Hynes R.O., Goetinck P.F. Syndecan-4 signals cooperatively with integrins in a Rho-dependent manner in the assembly of focal adhesions and actin stress fibers. Proc Natl Acad Sci USA. 96:1999;2805-2810.
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The ability of β1 and β3 integrins to increase Rho activity is assessed. Over-expression of β3, but not β1 in CHO cells, results in increased Rho-GTP levels. Substitution of the β1 extracellular I-domain-like sequence with the corresponding sequences from the β3 subunit confers the ability of β1 to activate Rho, indicating that the integrin extracellular domain is important.
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•], this paper explores which integrin β subunit is responsible for the increase in Rho activity that occurs after the initial dip following integrin ligation. Using β1 null cells in which β1 or β3 are expressed, the authors find that β1 integrins stimulate Rho activity but β3 has no effect. This result is the opposite from that obtained by Miao et al. and may reflect the different cells lines used. In both studies, the extracellular domain determined the response.
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•], this paper explores which integrin β subunit is responsible for the increase in Rho activity that occurs after the initial dip following integrin ligation. Using β1 null cells in which β1 or β3 are expressed, the authors find that β1 integrins stimulate Rho activity but β3 has no effect. This result is the opposite from that obtained by Miao et al. and may reflect the different cells lines used. In both studies, the extracellular domain determined the response.
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