Abstract
Caenorhabditis elegans sur-8 encodes a positive regulator of Ras signaling. We investigated the mechanism by which the human Sur-8 homolog can positively regulate Ras-MAP kinase signaling in mammalian cells. Sur-8 expression enhances Ras- or EGF-induced Raf and ERK activation but has no effect on ERK activation induced by active Raf or MEK. Furthermore, Sur-8 expression does not increase AKT or JNK activation. Sur-8 interacts with Ras and Raf and is able to form a ternary complex with the two proteins. Thus, Sur-8 may function as a scaffold that enhances Ras-MAP kinase signal transduction by facilitating the interaction between Ras and Raf.
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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Adaptor Proteins, Signal Transducing*
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Blotting, Western
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Caenorhabditis elegans Proteins*
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Carrier Proteins / metabolism*
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Cell Line
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DNA, Complementary / metabolism
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Dose-Response Relationship, Drug
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Enzyme Activation
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Epidermal Growth Factor / metabolism
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Glutathione Transferase / metabolism
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Humans
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MAP Kinase Signaling System*
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Plasmids
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Precipitin Tests
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Protein Binding
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Proto-Oncogene Proteins c-raf / metabolism*
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Signal Transduction
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Transfection
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Two-Hybrid System Techniques
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Up-Regulation
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ras Proteins / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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Caenorhabditis elegans Proteins
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Carrier Proteins
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DNA, Complementary
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Proto-Oncogene Proteins
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soc-2 protein, C elegans
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Epidermal Growth Factor
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Glutathione Transferase
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AKT1 protein, human
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Proto-Oncogene Proteins c-raf
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ras Proteins