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

Genes Dev. 2000 Apr 15;14(8):895-900.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Blotting, Western
  • Caenorhabditis elegans Proteins*
  • Carrier Proteins / metabolism*
  • Cell Line
  • DNA, Complementary / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Epidermal Growth Factor / metabolism
  • Glutathione Transferase / metabolism
  • Humans
  • MAP Kinase Signaling System*
  • Plasmids
  • Precipitin Tests
  • Protein Binding
  • Protein Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-raf / metabolism*
  • Signal Transduction
  • Transfection
  • Two-Hybrid System Techniques
  • Up-Regulation
  • ras Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • DNA, Complementary
  • Proto-Oncogene Proteins
  • soc-2 protein, C elegans
  • Epidermal Growth Factor
  • Glutathione Transferase
  • AKT1 protein, human
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-raf
  • ras Proteins