Abstract
The Ras-related small GTPase RalA is involved in controlling actin cytoskeletal remodelling and vesicle transport in mammalian cells. We identified the mammalian homologue of Sec5, a subunit of the exocyst complex determining yeast cell polarity, as a specific binding partner for GTP-ligated RalA. Inhibition of RalA binding to Sec5 prevents filopod production by tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) and by activated forms of RalA and Cdc42, signalling intermediates downstream of these inflammatory cytokines. We propose that the RalA-exocyst complex interaction integrates the secretory and cytoskeletal pathways.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Binding Sites
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COS Cells
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Cytoskeleton / physiology
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Cytoskeleton / ultrastructure
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Exocytosis / drug effects
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Exocytosis / physiology*
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GTP Phosphohydrolases / chemistry
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GTP Phosphohydrolases / physiology*
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Humans
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Interleukin-1 / pharmacology
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K562 Cells
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Membrane Proteins / chemistry
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Membrane Proteins / physiology*
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Protein Binding
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Pseudopodia / drug effects
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Pseudopodia / physiology*
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Pseudopodia / ultrastructure
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Rats
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Signal Transduction
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Tumor Necrosis Factor-alpha / pharmacology
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Vesicular Transport Proteins
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cdc42 GTP-Binding Protein / physiology
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ral GTP-Binding Proteins*
Substances
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Exoc2 protein, rat
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Interleukin-1
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Membrane Proteins
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Tumor Necrosis Factor-alpha
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Vesicular Transport Proteins
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GTP Phosphohydrolases
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RALA protein, human
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Rala protein, rat
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cdc42 GTP-Binding Protein
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ral GTP-Binding Proteins