Sandra RossieProfessor of Biochemistry Investigators : Area: The structure, regulation, and function of protein Ser/Thr phosphatase 5 |
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Reversible phosphorylation is an important and common mechanism for regulating a wide variety of processes in response to incoming signals such as hormones and neurotransmitters, enviromental changes or cell damage. In contrast to our knowledge of protein kinases and their roles in these processes, we know far less about protein phosphatases and their regulation. Protein phosphatase 5 (PP5) is a recently described member of the largest Ser/Thr protein phosphatase family, with a unique N-terminal domain that inhibits PP5 activity and binds other proteins PP5 has been implicated in signal transduction pathways controlling cell growth, differentiation and apoptosis, or programmed cell death. Little is known, however, about the physiological substrates for PP5 or how its activity may be regulated.
We use biochemical and molecular approaches to define the role and regulation of PP5 in brain and other tissues. Projects include defining the structural basis for controlling PP5 activity and potential regulators of PP5 activity. We are also using a proteomics approach to identify physiological substrates for PP5. We focus on the role of PP5 in neurons and in cancer cells, since the pathways in which PP5 may function are key players in neurodegenerative diseases and in tumor cell proliferation.
Selected Publications:
- Rossie, S., Jayachandran, H. and Meisel, R.L. Cellular co-localization of protein phosphatase 5 and glucocorticoid receptors in rat brain. Brain Res. 1111:1-11. (2006).
- Luo, Q., Tang, K., Yang, F., Elias, A., Shen, Y., Moore, R.J., Zhao, R., Hixson, K.K., Rossie, S.S. and Smith, R.D. More sensitive and quantitative proteomic measurements using very low flow rate porous silica monolithic LC columns with electrospray ionization-mass spectrometry. J. Proteome. Res. 5:1091-7 (2006).
- Messner, D.J., Romeo, C., Boynton, A. and Rossie, S. Inhibition of PP2A, but not PP5, mediates p53 activation by low levels of okadaic acid in rat liver epithelial cells. J Cell Biochem. 99:241-255. (2006).
- Gentile, S., Darden, T., Erxleben, C., Romeo, C., Russo, A., Martin, N., Rossie, S. and Armstrong, D.L. Rac GTPase signaling through the PP5 protein phosphatase. Proc. Natl. Acad. Sci. USA 103:5202-6 (2006).
- Yan, F., M. He, J. M. Hogan, S. S. Rossie and S. A. McLuckey. Targeted biomarker detection via whole protein ion trap tandem mass spectrometry: thymosin beta(4) in a human lung cancer cell line. J. Mass Spectrom. 40:444-451 (2005).
- Liu, F., K. Iqbal, I. Grundke-Iqbal, S. Rossie and C. X. Gong. Dephosphorylation of tau by protein phosphatase. 5: impairment in Alzheimer's disease. J. Biol. Chem. 280:1790-1796 (2005).
- Manaves, V., Wuxuan, Q., Bauer, A.L., Rossie, S., Kobayash,i M. and Rane, S. Calcium and Vitamin D increase mRNA levels for the growth control hIKI channel in human epiderman keratinocytes but functional channels are not observed. BMC Dermatology 4:7 (2004).
- Gong, C.X., Liu, F., Wu, W., Rossie, S., Wegiel, J., Li, L., -Iqbal, I.G. and Iqbal, K. Dephosphorylation of microtubule-associated protein tau by protein phosphatase 5. J. Neurochemistry 88:298-310 (2004).
- Jeong, J.-Y., Johns, J., Sinclair, C., Park, J.-M. and Rossie, S. Characterization of Saccharomyces cerevisiaeprotein Ser/Thr phosphatase T1 and comparison to its mammalian homolog PP5. BMC Cell Biology 4:3 (2003).
- Erxleben, C., Everhart, A., Florance, H., Bauer, M., Alcorta, D., Romeo, C., Rossie, S., Shipston, M.J. and Armstrong, D.L. Interacting effects of N terminal variation and strex exon splicing on rSlo potassium channel regulation by calcium, phosphorylation and oxidation. J. Biol. Chem. 277:27045-27052 (2002).
- Bahl, R, Bradley, K.C., Thompson, K.J., Swain, Rossie, S. andMeisel, R.L. Localization of protein Ser/Thr phosphatase 5 in rat brain. Mol. Brain Research. 90:101-109 (2001).
- Rossie, S. Regulation of voltage-sensitive ion channels by phosphorylation. Advances in Second Messenger and Phosphoprotein Research 33 (Armstrong, D. and Rossie, S. eds.) Academic Press, San Diego, CA. (1999).
- Sinclair, C., Borchers, C., Parker, C., Tomer, K., Charbonneau, H. and Rossie, S. The tetratricopeptide repeat domain and a C-terminal region control the activity of Ser/Thr protein phosphatase 5. J. Biol. Chem. 274:23666-23672 (1999).
