Identification of Functionally Distinct Regions That Mediate Biological Activity of the Protein Kinase A Homolog Tpk2*
- ‡Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093-0375 and the §Division of Biological Sciences, Section of Molecular Biology, and the University of California San Diego Moores Cancer Center, University of California, San Diego, La Jolla, California 92093-0347
- ↵2 To whom correspondence may be addressed: Dept. of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Dr., MC 0375, La Jolla, CA 92093-0375. Tel.: 858-822-0469; Fax: 858-534-7042; E-mail: gghosh{at}ucsd.edu.
- ↵3 To whom correspondence may be addressed: Division of Biological Sciences, Section of Molecular Biology, and UCSD Moores Cancer Center, University of California, San Diego, 9500 Gilman Dr., MC 0347, La Jolla, CA 92093-0347. Tel.: 858-822-2442; Fax: 858-534-0555; E-mail: lpillus{at}ucsd.edu.
Abstract
Kinases regulate key signaling processes that are increasingly implicated in development and disease. Kinase modulators have become important therapeutic tools and often target catalytic domains that are among the most structurally and functionally conserved regions of these enzymes. Such therapies lose efficacy as mutations conferring resistance arise. Because interactions between distinct and often distant regions of kinases can be critical, we took an unbiased genetic approach to identify sites within the protein kinase A homolog Tpk2 that contribute to its biological activity. Because many of these map outside the conserved core, this approach should be broadly useful in identifying new, more kinase-specific therapeutic targets.
- Received May 16, 2007.
- Revision received October 4, 2007.
- The American Society for Biochemistry and Molecular Biology, Inc.
