The objective of this application is to understand the role of protein phosphatase 5 (PP5) in GR signaling as a molecular chaperone and in regulating signal transduction by steroid receptors and other molecules. Specifically, Aim 1 will define at what point of the GR signaling pathway PP5 is required;
Aim 2 will test whether PP5 regulates the phosphorylation state of the GR and other proteins in the GR heterocomplex;
Aim 3 will test whether PP5 has a general function as a molecular chaperone of other proteins associated with hsp90.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK055877-02
Application #
2906414
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
Margolis, Ronald N
Project Start
1998-09-15
Project End
2002-07-31
Budget Start
1999-08-01
Budget End
2000-07-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of South Alabama
Department
Pharmacology
Type
Schools of Medicine
DUNS #
City
Mobile
State
AL
Country
United States
Zip Code
36688
Ramsey, Andrew J; Russell, Lance C; Chinkers, Michael (2009) C-terminal sequences of hsp70 and hsp90 as non-specific anchors for tetratricopeptide repeat (TPR) proteins. Biochem J 423:411-9
Gerges, Nashaat Z; Tran, Irwin C; Backos, Donald S et al. (2004) Independent functions of hsp90 in neurotransmitter release and in the continuous synaptic cycling of AMPA receptors. J Neurosci 24:4758-66
Ramsey, Andrew J; Chinkers, Michael (2002) Identification of potential physiological activators of protein phosphatase 5. Biochemistry 41:5625-32
Galigniana, Mario D; Harrell, Jennifer M; Murphy, Patrick J M et al. (2002) Binding of hsp90-associated immunophilins to cytoplasmic dynein: direct binding and in vivo evidence that the peptidylprolyl isomerase domain is a dynein interaction domain. Biochemistry 41:13602-10
Chinkers, M (2001) Protein phosphatase 5 in signal transduction. Trends Endocrinol Metab 12:28-32
Kang, H; Sayner, S L; Gross, K L et al. (2001) Identification of amino acids in the tetratricopeptide repeat and C-terminal domains of protein phosphatase 5 involved in autoinhibition and lipid activation. Biochemistry 40:10485-90
Ramsey, A J; Russell, L C; Whitt, S R et al. (2000) Overlapping sites of tetratricopeptide repeat protein binding and chaperone activity in heat shock protein 90. J Biol Chem 275:17857-62
Wu, S; Moore, T M; Brough, G H et al. (2000) Cyclic nucleotide-gated channels mediate membrane depolarization following activation of store-operated calcium entry in endothelial cells. J Biol Chem 275:18887-96
Russell, L C; Whitt, S R; Chen, M S et al. (1999) Identification of conserved residues required for the binding of a tetratricopeptide repeat domain to heat shock protein 90. J Biol Chem 274:20060-3