Critical contribution of linker proteins to Raf kinase activation.
Genetic analysis of Ras signaling has unveiled the participation of non-enzymatic accessory proteins in signal transmission. These proteins, KSR, CNK, and Sur-8, can interact with multiple core components of the Ras/MAP kinase cascade and may contribute to the structural organization of this cascade. However, the precise biochemical nature of the contribution of these proteins to Ras signaling is currently unknown. Here we show directly that CNK and KSR are required for stimulus dependent Raf kinase activation. CNK is required for membrane recruitment of Raf, while KSR is likely required to couple Raf to upstream kinases. These results demonstrate that CNK and KSR are integral components of the cellular machinery mediating Raf activation.
Anselmo
Anthony N
AN
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Bumeister
Ron
R
Thomas
Jackie M
JM
White
Michael A
MA
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D016895:Culture Media, Serum-Free; D004330:Drosophila; D029721:Drosophila Proteins; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D011905:Genes, ras; D019476:Insect Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000235:genetics; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; C115753:CNK protein, Drosophila; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D016895:Culture Media, Serum-Free; D029721:Drosophila Proteins; D019476:Insect Proteins; D012330:RNA, Double-Stranded; C113520:soc-2 protein, C elegans; D011494:Protein Kinases; C097199:KSR-1 protein kinase; D019908:Proto-Oncogene Proteins c-raf; D020928:Mitogen-Activated Protein Kinases