The leucine-rich repeat protein SUR-8 enhances MAP kinase activation and forms a complex with Ras and Raf.

Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109 USA.
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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Blotting, Western, Caenorhabditis elegans Proteins, Carrier Proteins, Cell Line, DNA, Complementary, Dose-Response Relationship, Drug, Enzyme Activation, Epidermal Growth Factor, Glutathione Transferase, Humans, MAP Kinase Signaling System, Plasmids, Precipitin Tests, Protein Binding, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Proto-Oncogene Proteins c-raf, Signal Transduction, Transfection, Two-Hybrid System Techniques, Up-Regulation, ras Proteins
Genes Dev. Apr. 15, 2000; 14(8);895-900 [PUBMED:10783161]
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