CNK, a RAF-binding multidomain protein required for RAS signaling.
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.
Therrien
M
M
Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley 94720-3200, USA.
Wong
A M
AM
Rubin
G M
GM
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D019143:Evolution, Molecular; D005123:Eye / Q000737:chemistry / Q000254:growth & development; D005799:Genes, Dominant; D016153:Genes, Suppressor; D006801:Humans; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D007365:Intercellular Junctions / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010641:Phenotype; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D014921:Wings, Animal / Q000254:growth & development; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C115753:CNK protein, Drosophila; D002352:Carrier Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D011494:Protein Kinases; C097199:KSR-1 protein kinase; D020794:Receptor Protein-Tyrosine Kinases; D019908:Proto-Oncogene Proteins c-raf; D018631:ras Proteins