Reversible phosphorylation is an important and common mechanism for regulating many functions in brain including electrical excitation and the consolidation of memory. Much is known concerning the identity and regulation of protein kinases that participate in these processes, but far less is known about the protein phosphatases that are the obligate partners of kinases in signal transduction. Our long-term goal is to understand the function and regulation of Ser/Thr protein phosphatase 5 in the central nervous system. We recently purified this enzyme as a lipid-activated enzyme from brain. Although little is known about the biological function of protein phosphatase 5, studies in non-neuronal cells have implicated this enzyme in hormone signaling pathways controlling gene expression, ion channel regulation and other processes that are central to the function of neurons. In order to understand the role of this enzyme in brain, we plan to identify its cellular targets in neurons and endocrine cells. In addition, we will define signaling pathways in which protein phosphatase 5 participates in brain to further our understanding of how hormones and neurotransmitters control neuronal function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS031221-13
Application #
7082863
Study Section
Special Emphasis Panel (ZRG1-MDCN-1 (02))
Program Officer
Stewart, Randall R
Project Start
1992-03-15
Project End
2008-05-31
Budget Start
2006-06-01
Budget End
2008-05-31
Support Year
13
Fiscal Year
2006
Total Cost
$306,189
Indirect Cost
Name
Purdue University
Department
Biochemistry
Type
Schools of Earth Sciences/Natur
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907
Chatterjee, Anindya; Wang, Ling; Armstrong, David L et al. (2010) Activated Rac1 GTPase translocates protein phosphatase 5 to the cell membrane and stimulates phosphatase activity in vitro. J Biol Chem 285:3872-82
Ham, Bryan M; Jayachandran, Hemalatha; Yang, Feng et al. (2010) Novel Ser/Thr protein phosphatase 5 (PP5) regulated targets during DNA damage identified by proteomics analysis. J Proteome Res 9:945-53
Sanchez-Ortiz, Efrain; Hahm, Byoung Kwon; Armstrong, David L et al. (2009) Protein phosphatase 5 protects neurons against amyloid-beta toxicity. J Neurochem 111:391-402
Jeong, Jee-Yeong; Johns, Jeremiah; Sinclair, Christopher et al. (2003) Characterization of Saccharomyces cerevisiae protein Ser/Thr phosphatase T1 and comparison to its mammalian homolog PP5. BMC Cell Biol 4:3