Protein phosphatase 4 (PP4) is a protein phosphatase 2A (PP2A)-related serine/threonine phosphatase. PP2A is involved in regulating diverse cellular processes such as cell signaling, cell cycle regulation, apoptosis, and tumorigenesis; however, little is known about the functions of PP4. Many of the above functions identified for PP2A were based on the studies using okadaic acid, an inhibitor previously thought to be PP2A-specific, but now known to inhibit PP4 at similar concentrations. Therefore, some of the previously identified functions assigned to PP2A may in fact be the functions for PP4. PP4 binds to and activates Rel/NF-KB proteins. Rel/NF-KB proteins are pivotal molecules that are involved in a plethora of cellular responses such as gene regulation, apoptosis, cell cycle, cell proliferation, oncogenesis, inflammation, and cell adhesion/migration. Our recent results also indicate that PP4 activates cJun N-terminal kinase (JNK). JNK subgroup belongs to the mitogen-activated protein kinase (MAPK) superfamily. JNK kinase cascade is involved in apoptosis, differentiation, cell proliferation, oncogenesis, and various stress responses such as inflammatory responses and heart ischemia/reperfusion. Understanding the functions and regulation of PP4, as well as the underlying mechanisms of NF-KB/JNK activation by PP4 will lead to a better understanding of the NF-KB, JNK and PP4 signaling pathways.
The specific aims are the following: (1) to study the regulation andfunction of PP4, (2) to determine the role of PP4 in NF-KB activation, and (3) to determine the role of PP4 in JNK activation, The information derived from this study should provide important information for a better design of therapeutic drugs for inflammatory diseases, cancers, and cardiac diseases.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA087076-05
Application #
7046096
Study Section
Physiological Chemistry Study Section (PC)
Program Officer
Yassin, Rihab R,
Project Start
2002-04-01
Project End
2008-03-31
Budget Start
2006-04-01
Budget End
2008-03-31
Support Year
5
Fiscal Year
2006
Total Cost
$261,595
Indirect Cost
Name
Baylor College of Medicine
Department
Pathology
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
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