Pic Of The Day
Posted by rob on November 23, 2004 under Uncategorized | 
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An airplane plane flies past the moon in the skies of the German southern town of Nuremberg.
Protein Plays Different Roles In Growth Of Normal And Cancerous Mouse Cell Lines
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Protein Plays Different Roles In Growth Of Normal And Cancerous Mouse Cell Lines
Researchers at the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), have found that inhibition of the same protein produces different effects in mouse cell lines depending on whether those cell lines expressing normal or cancerous forms of Kit, a cell surface receptor. These findings, appearing in the journal Blood online on November 12, reveal a potential new target for treating certain blood cell disorders.
Kit is critical for the development of certain blood cells, and mutations in Kit are associated with several diseases in mast cells, a type of white blood cell involved in immune responses. Gleevec, a drug that inhibits Kit and other related proteins, has been useful in the treatment of diseases associated with these proteins, including gastrointestinal stromal cell tumors and chronic myeloid leukemia. However, an activating mutation in Kit commonly found in mast cell disease and some forms of acute myeloid leukemia is resistant to Gleevec. Therefore, one potential method of circumventing a drug-resistant form of Kit would be to target one or more of the proteins activated by it.
NCI researchers Diana Linnekin, Ph.D., and Tanya Jelacic, Ph.D., found that inhibition of one such Kit activated protein, PKCδ <PKCdelta> (a member of a family of protein kinases involved in cell signaling), reduced the growth of a mouse mast cell line expressing mutant Kit by approximately 40 percent, while the growth of normal mast cells was not inhibited. “This is the first demonstration of a function change in PKCδ <PKCdelta> resulting from an oncogenic mutation in a growth factor receptor,” said Linnekin.
These results suggest that PKCδ <PKCdelta> may be a therapeutic target for diseases associated with mutations in Kit, since anti-PKCδ <PKCdelta> drugs would specifically inhibit the growth of mutated cells and not affect normal ones. “This work is a promising study on cancer inhibition,” said Linnekin. “Dr. Jelacic and I believe that follow-up work with human cell lines, as well as work in mouse models of cancer, would be definitely worthwhile.”
For more information about cancer, visit the NCI Web site at http://www.cancer.gov or call NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
Editor’s Note: The original news release can be found here.
http://www.sciencedaily.com/releases/2004/11/041118112702.htm
Kinase Assay By Mass Spec – New method is simpler and faster than traditional kinase assays
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| MAUREEN ROUHI | |||||
Peptides immobilized on a surface plus mass spectrometry equals rapid and direct analysis of kinase activities, a new study shows [Angew. Chem. Int. Ed., 43, 5973 (2004)]. Developed by University of Chicago researchers Dal-Hee Min, Jing Su, and Milan Mrksich, the strategy avoids the complications of traditional kinase assays, including use of radioactive labels or antibody binding. Kinases mediate the phosphorylation of specific substrates. They have many regulatory functions, and assaying kinase activity is key in many research areas, including drug discovery. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, the Chicago team evaluates kinase activity from the spectra of peptides, immobilized on a gold substrate, before and after exposure to a kinase-mediated phosphorylation. In the after spectrum, the mass peak of the kinase’s substrate is replaced by that of the product. The team applied the method to six kinases. The kinase reaction yielded a mass change of 80, due to addition of a phosphate group to each substrate. Multiple kinase activities can be measured by exposing a peptide array sequentially to different kinases. The assay also can be used to measure kinase inhibition. Results for the inhibition of the kinase Ab1 by the anticancer drug Gleevec are within the range of values reported in the literature. “The most significant aspect of our work has been the development of surfaces that allow both quantitative assays of enzyme activity and readout by mass spectrometry,” Mrksich says. “These tailored substrates simplify the use of mass spectrometry for analyzing enzymatic activities and therefore move this technique closer to routine use in research laboratories.” |
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| Chemical & Engineering News ISSN 0009-2347 Copyright © 2004 |
