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
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Animals
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Carrier Proteins / chemistry
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism*
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Cell Differentiation
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Cell Line
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Cell Survival
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Drosophila Proteins*
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Drosophila melanogaster / genetics*
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Drosophila melanogaster / growth & development
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Drosophila melanogaster / metabolism
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Evolution, Molecular
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Eye / chemistry
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Eye / growth & development
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Genes, Dominant
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Genes, Suppressor
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Humans
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Insect Proteins / chemistry
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Insect Proteins / genetics*
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Insect Proteins / metabolism*
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Intercellular Junctions / metabolism
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Molecular Sequence Data
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Mutagenesis
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Phenotype
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Phosphorylation
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Protein Kinases / genetics*
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Proto-Oncogene Proteins c-raf / metabolism*
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Receptor Protein-Tyrosine Kinases / metabolism
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Signal Transduction*
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Wings, Animal / growth & development
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ras Proteins / antagonists & inhibitors
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ras Proteins / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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CNK protein, Drosophila
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Carrier Proteins
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Drosophila Proteins
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Insect Proteins
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Protein Kinases
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KSR-1 protein kinase
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Receptor Protein-Tyrosine Kinases
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Proto-Oncogene Proteins c-raf
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ras Proteins
Associated data
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GENBANK/AF100152
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GENBANK/AF100153