The phosphoryloration and dephosphoryloration of serine and threonine residues in proteins are essential steps that regulate various cellular processes. However, little is known about the signal transduction pathways in T. brucei. The serine/threonine protein phosphatase 5 (PP5) is a member in the PPP family protein and is structurally distinct for its N-terminal tetratricopeptide repeat (TPR) domains. The TPR domain of PP5 is involved in protein protein interactions and stimulates the activity of PP5 by interacting with polyunsaturated fatty acids such as arachidonic acid (AA). Recent discoveries have pointed to possible roles for PP5 in diverse signaling pathways. In order to characterize the physiological activator(s) and to elucidate the mechanism of the activation of TbPP5, recombinant TbPP5, different structural domains of TbPP5 and native TbPP5 from both the procyclic and bloodstream cells will be used for different phosphatase assays using different substrates, saturated, unsaturated fatty acids, their esters and an AA metabolite as the activator. The structural domain that interacts with the physiological activator to activate TbPP5 will also be determined. These will pin-point the mechanism of activation of TbPP5 under physiological conditions and possible reveal signal transduction pathways in the parasite and the biology of the parasite.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31GM069166-02
Application #
6839397
Study Section
Minority Programs Review Committee (MPRC)
Program Officer
Toliver, Adolphus
Project Start
2003-09-01
Project End
2007-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
2
Fiscal Year
2004
Total Cost
$32,998
Indirect Cost
Name
Meharry Medical College
Department
Microbiology/Immun/Virology
Type
Other Domestic Higher Education
DUNS #
041438185
City
Nashville
State
TN
Country
United States
Zip Code
37208
Jones, Candace; Anderson, Sedrick; Singha, Ujjal K et al. (2008) Protein phosphatase 5 is required for Hsp90 function during proteotoxic stresses in Trypanosoma brucei. Parasitol Res 102:835-44