Protein kinases mediate signaling throughout the cell and are regulated in a temporal and spatially defined manner. Recently, a combined chemical and genetic strategy has been developed to selectively inactivate kinases of interest in vivo. Extending this technique with photosensitive kinase inhibitors offers a means to control the activity of a wide range of kinases. To achieve temporally controlled kinase inactivation, a series of photocleavably masked inhibitors will be synthesized, where irradiation reveals the active inhibitor. To achieve spatially and temporally controlled kinase activation, a series of photoreversible covalent inhibitors will be synthesized, where irradiation abolishes inhibition. The two groups of inhibitors will be tested for their ability to turn kinases """"""""off"""""""" or """"""""on"""""""" both in vitro and in vivo. Together these inhibitors will be used to address an outstanding question in kinase regulation and should provide new insights into the nature of cell signaling in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
7F32AI010611-02
Application #
6372948
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Program Officer
Prograis, Lawrence J
Project Start
2000-07-01
Project End
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
2
Fiscal Year
2001
Total Cost
$34,832
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
660735098
City
Worcester
State
MA
Country
United States
Zip Code
01655
Fry, C J; Shogren-Knaak, M A; Peterson, C L (2004) Histone H3 amino-terminal tail phosphorylation and acetylation: synergistic or independent transcriptional regulatory marks? Cold Spring Harb Symp Quant Biol 69:219-26
Shogren-Knaak, Michael A; Fry, Christopher J; Peterson, Craig L (2003) A native peptide ligation strategy for deciphering nucleosomal histone modifications. J Biol Chem 278:15744-8