Inflammatory bowel disease reveals the kinase activity of KSR1.
Kinase suppressor of Ras-1 (KSR1) is a recently identified member of the EGFR-Ras-Raf-1-MAPK signaling pathway. A new study demonstrates that KSR1 protects intestinal epithelium from TNF-alpha-induced apoptosis, abrogating inflammatory bowel disease (IBD). Since its discovery, there has been disagreement as to whether KSR1 possesses intrinsic kinase activity. Using transgenic mouse models and genetically modified mouse colon epithelial cells, Polk and coworkers show that the kinase activity of KSR1 is off in normal colon epithelial cells, becoming activated only at the onset of IBD. They also provide strong evidence that KSR1 kinase activity is essential for anti-apoptotic protection of the intestinal epithelium. These new data in support of KSR1 as a kinase highlight an ongoing debate as to whether KSR1 does indeed serve as a specific kinase in transphosphorylating and transactivating c-Raf-1 toward MEK1.
Kolesnick
Richard
R
Laboratory of Signal Transduction, The Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. r-kolesnick@ski.mskcc.org
Xing
H Rosie
HR
D017209:Apoptosis; D003106:Colon / Q000201:enzymology; D004847:Epithelial Cells / Q000201:enzymology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000201:enzymology* / Q000473:pathology; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D008954:Models, Biological; D011494:Protein Kinases / Q000502:physiology*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation
D011494:Protein Kinases; C097199:KSR-1 protein kinase; D019908:Proto-Oncogene Proteins c-raf; D048369:MAP Kinase Kinase 1