The P.I. has previously demonstrated that a 36kDa Myelin Basic Protein Kinase (MBP Kinase) is activated during ceramide-induced apoptosis in HL60 promyelocytic leukemia cells. This kinase is activated in the subset of cells that have actually initiated apoptosis. Purification and microsequencing reveal that the kinase is derived from a previously identified Mammalian Sterile Twenty (MST) Kinase, two isoforms of which were cloned and characterized by the P.I.. The P.I. now plans to: 1) characterize the cellular regulation of MST kinases in response to stress/apoptotic signals; 2) characterize the physiological roles of these kinases using an inducible expression system and genetically engineered mutants and 3) characterize the signalling pathway that leads to activation of the MST kinases.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
3R29GM054713-04S1
Application #
6417977
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Kelty, Miriam F
Project Start
1997-08-01
Project End
2002-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
4
Fiscal Year
2001
Total Cost
$48,897
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
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Masiello, David; Cheng, Shinta; Bubley, Glenn J et al. (2002) Bicalutamide functions as an androgen receptor antagonist by assembly of a transcriptionally inactive receptor. J Biol Chem 277:26321-6
Lu, M L; Schneider, M C; Zheng, Y et al. (2001) Caveolin-1 interacts with androgen receptor. A positive modulator of androgen receptor mediated transactivation. J Biol Chem 276:13442-51