The binding of NK cells to lysis-sensitive (LS) target cells initiates a series of biochemical responses. Although most of the initiated pathways appear to participate during NK cell effector function, the induction of elevated cAMP levels may elicit a feedback regulatory system. This proposal seeks to further define how LS-target cell binding induces increased cellular accumulation of cAMP, and how this impacts upon NK cell effector capabilities. This proposal is divided into four specific aims, with the first three committed to understanding the mechanisms involved with elevating cAMP levels.
The first aim will characterize the relative contributions of increased adenylyl cyclase (AC) and decreased phosphodiesterase (PDE) activities to this increase.
The second aim will determine how receptor occupancy regulates AC activity.
The third aim i s to identify which PDE isoforms are operative in NK cells and how their activities are regulated after engagement of LS-targets.
The fourth aim will initiate the characterization of how elevated cAMP levels impact on the cytolytic capabilities of NK cells.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
7R15CA074354-02
Application #
6027556
Study Section
Special Emphasis Panel (ZRG2-IMB (01))
Program Officer
Finerty, John F
Project Start
1998-08-01
Project End
2002-07-31
Budget Start
1999-01-01
Budget End
2002-07-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Tennessee State University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
City
Nashville
State
TN
Country
United States
Zip Code
37209
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