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Scientists develop chemical switch for natural signaling molecules, opening new approach to biomedical research and drug design

at Scripps Research Institute and formerly Shokat's graduate student graduate at Princeton University where much of this research was undertaken.

Co-authors and collaborators on the research with Shokat, Bishop and Morgan are Jeffrey Ubersax, a graduate student and Justin Blethrow, research associate, in physiology and biochemistry at UCSF; graduate student Dejah Petsch and John Wood, PhD, professor, both in chemistry at Yale University; Mark Rose, PhD and Joe Tsien, PhD, both professors; graduate student Dina Matheos and post-doctoral researcher Elji Shimizu, all in molecular biology at Princeton University; Nathanael Gray and Peter Schultz at the Genomics Institute of the Novartis Foundation.

The research reported in Nature focused on the kinase Cdc28, needed for normal cell division. Trying to study such a kinase using genetic techniques that create a "knockout" yeast lacking the gene would not be possible, since disrupting cell division would be lethal, Shokat points out. The results from the collaboration between Morgan and Shokat revealed that the kinase activity of Cdc28 was most critical before cell separation. In contrast, genetic studies with temperature sensitive forms of Cdc28 suggested the most critical role was before the DNA duplication stage of the cell cycle. These results suggest that kinase activity is sensed during the cell cycle and inhibitors can precisely regulate this function, leading to different arrest points than those revealed by genetic studies.


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Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
24-Sep-2000


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