Inflammatory bowel disease reveals the kinase activity of KSR1 Journal Article
| Authors: | Kolesnick, R.; Xing, H. R. |
| Article Title: | Inflammatory bowel disease reveals the kinase activity of KSR1 |
| Abstract: | 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-α-induced apoptosis, abrogating inflammatory bowel disease (IBD) (see the related article beginning on page 1272). 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. |
| Keywords: | signal transduction; mitogen activated protein kinase; protein expression; unclassified drug; review; raf protein; nonhuman; note; protein function; mouse; metabolism; apoptosis; biological model; models, biological; mitogen activated protein kinase kinase 1; protein kinases; epidermal growth factor receptor; enzyme activation; enzymology; pathology; enzyme activity; physiology; transgenic mouse; disease model; enzyme phosphorylation; tumor necrosis factor alpha; transactivation; epithelium cell; epithelial cells; enteritis; ras protein; inflammatory bowel diseases; protein kinase; colon; map kinase kinase 1; kinase suppressor of ras 1; proto-oncogene proteins c-raf; colon mucosa; protection; trans-activation (genetics); ksr 1 protein kinase; ksr-1 protein kinase; intestine epithelium; humans; human; priority journal |
| Journal Title: | Journal of Clinical Investigation |
| Volume: | 114 |
| Issue: | 9 |
| ISSN: | 0021-9738 |
| Publisher: | American Society for Clinical Investigation |
| Date Published: | 2004-11-01 |
| Start Page: | 1233 |
| End Page: | 1237 |
| Language: | English |
| DOI: | 10.1172/jci23441 |
| PROVIDER: | scopus |
| PMCID: | PMC524240 |
| PUBMED: | 15520853 |
| DOI/URL: | |
| Notes: | J. Clin. Invest. -- Cited By (since 1996):18 -- Export Date: 16 June 2014 -- CODEN: JCINA -- Source: Scopus |
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