Keith K. Schlender
Telephone: (419) 383-4184, 383-4182
FAX: (419) 383-2871
- B.A., Chemistry, 1961, Westmar College, LeMars, Iowa
- M.S., Biochemistry, 1963, Michigan State University
- Ph.D., Biochemistry, 1966, Michigan State University
- Post-doctoral Fellow, Department of Biochemistry, University of Minnesota, 1966-1969
- Assistant Professor of Pharmacology and Therapeutics, Medical College of Ohio, 1969-1974
- Associate Professor of Pharmacology and Therapeutics, Medical College of Ohio, 1974-1981
- Professor of Physiology, Department of Physiology and Pharmacology, University of Toledo College of Medicine, Health Science Campus, 1981-present
- Dean of the College of Graduate Studies, Medical University of Ohio, 1990-2005
- Regulation of cell function by protein kinases and phosphatases.
The process of reversible protein phosphorylation-dephosphorylation is an important mechanism for the regulation of a numerous cellular processes. The extent of phosphorylation of specific proteins is determined by the relative activity of protein kinases and protein phosphatases. In many cases, the relevant kinase has been identified. However, our understanding of the regulation of the phosphorylation-dephosphorylation mechanism has been hindered by a lack of information about the protein phosphatases involved. For a number of years, my laboratory has been interested in the enzymology of protein kinases and protein phosphatases. Our past accomplishments have included the discovery of calcium and cyclic nucleotide-independent glycogen synthase kinases that phosphorylate and inactivate glycogen synthase and a class of protein phosphatase which is stimulated by polycations (now designated phosphatase 2A). More recently we have discovered a novel form of protein phosphatase 1 in heart muscle and a latent form of phosphatase 2A in skeletal muscle.
Currently our work is focused on two areas.
- Purification and characterization of latent myofibril protein phosphatase 1. The major form of protein phosphatase associated with the cardiac myofibril is a latent form of protein phosphatase 1 (phosphatase 1M). We have proposed that phosphatase 1M is a unique form of phosphatase 1 which may be specific for myofibril proteins. To test this hypothesis and to investigate the role of phosphatase 1M in the regulation of myofibril processes, we are purifying and characterizing phosphatase 1M. These studies include determining the subunit structure, determining the primary sequence of the regulatory subunit, and determining how the activity of the enzyme is regulated.
- Investigating the significance of phosphorylation-dephosphorylation in the regulation of cardiac C-protein function. Although C-protein has been recognized as a major myofibril phosphoprotein for many years, the function of C-protein and the significance of its phosphorylation remains unclear. Our efforts on C-protein are concentrated on determining the primary sequence of C-protein, determining what sites are phosphorylated in vivo, establishing how C-protein regulates myofibril function, and defining what domains are necessary for C-protein function.
- Schlender, K.K. and Bean, L.J. (1991): Phosphorylation of chicken cardiac C-protein by calcium/calmodulin-dependent protein kinase II. J. Biol. Chem. 266:2811-2817.
- Wang, W., Lane, R.D., and Schlender, K.K. (1992): Antibodies directed against synthetic peptides distinguish between the catalytic subunits of protein phosphatases 1 and 2A. Biochem. Biophys. Res. Commun. 185:657-662.
- Reimann, E.M., Peng, Z.-Y., Feng, Z., Pradhan, J., Schlender, K.K., and Trumbly, R.J. (1993): Glycogen synthase in Saccharomyces cerevisiae: Regulation by protein phosphatase 1. Adv. Prot. Phosphatases 7:173-182.
- Chu, Y., Wilson, S.E., and Schlender, K.K. (1994): A latent form of protein phosphatase 1alpha associated with bovine heart myofibrils. Biochim. Biophys. Acta 1208:45-54.
- Cai, L., Chu, Y., Wilson, S.E., and Schlender, K.K. (1995): A metal- dependent form of protein phosphatase 2A. Biochem. Biophys. Res. Commun. 208, 274-279.
- Grekinis, D., Reimann, E.M., and Schlender, K.K. (1995): Phosphorylation and inactivation of rat heart glycogen synthase by cAMP-dependent and cAMP- independent protein kinases. Int. J. Biochem. Cell. Biol. 27:565-573.
- Chu, Y., Lee, E.Y.C., and Schlender, K.K. (1996): Activation of protein phosphatase 1: Formation of a metalloenzyme. J. Biol. Chem. 271:2574-2577.
- Chu, Y., Lee, E.Y.C., Reimann, E.M., Wilson, S.E., and Schlender, K.K. (1996): Effect of activation of protein phosphatase 1 on sulfhydryl reactivity. Arch. Biochem. Biophys. Arch. Biochem. Biophys. 334:83-88.
- Guan, X., Wilson, S., Schlender, K.K., and Ruch, R.J. (1996): Gap junction disassembly and connexin43 dephosphorylation induced by 18beta- glycyrrhetinic acid. Mol. Carcinog. 16:157-164.
- Dignam, S.S., Koushik, J.S., Wang, J., Trumbly, R.J., Schlender, K.K., Lee, E.Y.C., and E.M. Reimann (1998): Purification and characterization of type 1 protein phosphatase from Saccharomyces cerevisiae: Effect of R73C mutation. Arch. Biochem. Biophys. 357:58-66.
- Mohamed, A.S., Dignam, J.D., and Schlender, K.K. (1998): Identification of protein kinase A and protein kinase C phosphorylation sites. Arch. Biochem. Biophys. 358:313-319.
- Hong, G., Trumbly, R.J., Reimann, E.M., and Schlender, K.K. (2000): Sds22p is a subunit of a stable isolatable form of protein phosphatase 1 (Glc7p) from Saccharomyces cerevisiae. Arch. Biochem. Biophys. 376:288-298.