Abstract

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.

  Funding Agency

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

  Institution

Name
University of South Alabama
Department
Pharmacology
Type
Schools of Medicine
DUNS #
City
Mobile
State
AL
Country
United States
Zip Code
36688

  Publications

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