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Multiple signal transduction pathways regulate TNF-induced actin reorganization in macrophages: inhibition of Cdc42-mediated filopodium formation by TNF.

Peppelenbosch, M; Boone, E; Jones, GE; van Deventer, SJ; Haegeman, G; Fiers, W; ... Ridley, AJ; + view all (1999) Multiple signal transduction pathways regulate TNF-induced actin reorganization in macrophages: inhibition of Cdc42-mediated filopodium formation by TNF. J Immunol , 162 (2) 837 - 845.

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Abstract

TNF is known to regulate macrophage (Mphi) migration, but the signaling pathways mediating this response have not been established. Here we report that stimulation of the 55-kDa TNF receptor (TNFR-1) induced an overall decrease in filamentous actin (F-actin), inhibited CSF-1- and Cdc42-dependent filopodium formation, and stimulated macropinocytosis. Using a panel of TNFR-1 mutants, the regions of the receptor required for each of these responses were mapped. The decrease in F-actin required both the death domain and the membrane proximal part of the receptor, whereas inhibition of filopodium formation and increased pinocytosis were only dependent upon a functional death domain. When the TNF-induced decrease in F-actin was inhibited using either receptor mutants or the compound D609, TNF-stimulated actin reorganization at the cell cortex became apparent. This activity was dependent upon the FAN-binding region of TNFR-1. We conclude that different domains of TNFR-1 mediate distinct changes in the Mphi cytoskeleton, and that the ability of TNF to inhibit Mphi chemotaxis may be due to decreased filopodium formation downstream of Cdc42.

Type:Article
Title:Multiple signal transduction pathways regulate TNF-induced actin reorganization in macrophages: inhibition of Cdc42-mediated filopodium formation by TNF.
Location:UNITED STATES
Language:English
Keywords:Actins, Animals, Antigens, CD, Calcium-Calmodulin-Dependent Protein Kinases, Cell Cycle Proteins, Cell Membrane, Cell Migration Inhibition, Cells, Cultured, GTP-Binding Proteins, Leukemia P388, Macrophage Colony-Stimulating Factor, Macrophages, Mice, Mitogen-Activated Protein Kinases, Peptide Fragments, Pinocytosis, Pseudopodia, Receptors, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Type I, Signal Transduction, Tetradecanoylphorbol Acetate, Tumor Necrosis Factor-alpha, cdc42 GTP-Binding Protein, p38 Mitogen-Activated Protein Kinases
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of)

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