CNK, a RAF-binding multidomain protein required for RAS signaling

Cell. 1998 Oct 30;95(3):343-53. doi: 10.1016/s0092-8674(00)81766-3.

Abstract

Kinase suppressor of ras (ksr) is required for efficient signal transmission within the RAS/MAPK cascade. A screen for mutations that modify a ksr-dependent phenotype identified a novel gene, connector enhancer of ksr (cnk), that functions upstream or in parallel to RAF in the RAS pathway. cnk encodes a protein containing several protein-protein interaction domains, suggesting that it brings different signaling molecules together. CNK is required in multiple receptor tyrosine kinase pathways where it appears to be a tyrosine phosphorylation target. Finally, CNK physically interacts with RAF and appears to localize to cell-cell contact regions. Together, these findings suggest that CNK is a novel component of a RAS-dependent signaling pathway that regulates RAF function and/or targets RAF to a specific subcellular compartment upon RAS activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Cell Differentiation
  • Cell Line
  • Cell Survival
  • Drosophila Proteins*
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism
  • Evolution, Molecular
  • Eye / chemistry
  • Eye / growth & development
  • Genes, Dominant
  • Genes, Suppressor
  • Humans
  • Insect Proteins / chemistry
  • Insect Proteins / genetics*
  • Insect Proteins / metabolism*
  • Intercellular Junctions / metabolism
  • Molecular Sequence Data
  • Mutagenesis
  • Phenotype
  • Phosphorylation
  • Protein Kinases / genetics*
  • Proto-Oncogene Proteins c-raf / metabolism*
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Signal Transduction*
  • Wings, Animal / growth & development
  • ras Proteins / antagonists & inhibitors
  • ras Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • CNK protein, Drosophila
  • Carrier Proteins
  • Drosophila Proteins
  • Insect Proteins
  • Protein Kinases
  • KSR-1 protein kinase
  • Receptor Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-raf
  • ras Proteins

Associated data

  • GENBANK/AF100152
  • GENBANK/AF100153