Signal Transduction by Tyrosine Kinases

There are approximately 90 tyrosine kinases in the human genome, and they are important regulators of growth and differentiation in normal mammalian cells. Tyrosine kinases are normally under tight control and have low basal activity; they are activated transiently in response to specific stimuli. Inappropriate activation of tyrosine kinase signaling (by mutation, overexpression, or chromosomal rearrangement) often occurs in human cancers. For example, human chronic myelogenous leukemia (CML) is characterized by a chromosomal translocation that leads to deregulation of the Abl tyrosine kinase. In May 2001, the Food and Drug Administration approved the first small-molecule tyrosine kinase inhibitor, imatinib (Gleevec), which has proven to be an effective therapy for CML. The development of drugs such as Gleevec indicates that an understanding of oncogenic tyrosine kinases can lead to the design of new strategies for cancer treatment. The major research goals of our laboratory are: (1) to understand how tyrosine kinases recognize their target proteins in cells; (2) to determine the regulatory mechanisms that control tyrosine kinase activity; and (3) to develop strategies to block the action of oncogenic tyrosine kinases.

Please use these links to learn more about the research in the Miller lab:

Regulation of nonreceptor tyrosine kinases

Nature 385, 650-653 (1997).
J. Biol. Chem. 275, 2721-2726 (2000).
Biochemistry 48, 10956-10962 (2009).

Kinase evolution and engineering

Nature 451, 783-788 (2008).
Proc. Natl. Acad. Sci. USA 105, 9674-9 (2008).
PLoS ONE 6, e19296 (2011).

Insulin-like growth factor I receptor

Nature Stuctural Biol. 8, 1058-1063 (2001).
J. Biol. Chem. 281, 23785-23791 (2006).
EMBO Journal 27, 1985-1994 (2008).

Tyrosine kinase signaling in cancer cells

Oncogene 20, 6057-6065 (2001).
Oncogene 24, 5656-5664 (2005).
Proc. Natl. Acad. Sci. USA 105, 12463-8 (2008).

Full list of publications:

Publications, 1987-2013

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