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Martin C. Schmidt, Ph.D.
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Associate Professor
W1247 BSTWR
200 Lothrop Street
Pittsburgh, Pennsylvania 15261
Phone: (412) 648-9243
Fax: (412) 624-1401
E-mail: mcs2@pitt.edu
Lab Phone: (412) 648-9380
Lab Website
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Biography
Dr. Schmidt is an Associate Professor in Microbiology and Molecular Genetics and Director of the Graduate Program in Biochemistry and Molecular Genetics. He received his Ph.D in Biochemistry from the University of California at Berkeley in 1985 where he studied E. coli RNA polymerase with Mike Chamberlin. After postdoctoral studies with Arnold Berk at UCLA, he joined the University of Pittsburgh School of Medicine in 1990.
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Research
Our recent studies have focused on the Snf1 kinase of yeast. The mammalian homologue of Snf1 is the AMP-activated protein kinase, an important therapeutic target for type II diabetes. Biochemical and genetic experiments have shown that Snf1 kinase is regulated by phosphorylation of the conserved threonine residue in the kinase activation loop. We have developed a phosphopeptide antibody that specifically recognizes the phosphorylated (active) form of Snf1 kinase. We have used the antibody to demonstrate that Snf1 is activated by three distinct upstream kinases called Sak1, Tos3 and Elm1. We would like to determine the mechanism by which glucose abundance determines the phosphorylation status of the Snf1 activation loop. Our most recent work has shown that the Snf1-activating kinases are not themselves regulated by glucose. Instead, it is the DEphosphorylation of the Snf1 activation loop that responds to changes in glucose abundance. Future studies will focus on understanding the molecular mechanisms regulating the dephosphorylation reaction.
The long term goal of the lab is to identify all the components of the glucose signaling pathway in yeast and to understand how they interact in order to regulate gene expression and cellular metabolism. These studies will provide a better understanding of glucose-mediated regulation of cellular metabolism and have important implications for designing novel treatments for patients with diabetes.
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Selected Publications
- Shirra,M.K., R.R. McCartney, C. Zhang, K.M. Shokat, M.C. Schmidt and K.M. Arndt. 2008. "A Chemical-Genomics Study Identifies Snf1 as a Repressor of Gcn4 Translation" J. Biol. Chem. 283: 35889-35898. | Abstract
- Rubenstein, E.M., R.R. McCartney, C. Zhang, K.M. Shokat, M.K. Shirra, K.M. Arndt and M.C. Schmidt (2008) "Access Denied: Snf1 Activation Loop Phosphorylation is Controlled by Availability of the Phosphorylated Threonine 210 to the PP1 Phosphatase" J. Biol. Chem. 283: 222-230. | Abstract
- Rubenstein, E.M. and M.C. Schmidt 2007. "Mechanisms regulating the protein kinases of Saccharomyces cerevisiae" Eukaryotic Cell 6:571-83 | Abstract
- Elbing, K., E.M. Rubenstein, R.R. McCartney and M.C. Schmidt. 2006. "Subunits of the SNF1 kinase heterotrimer show interdependence for association and activity" J. Biol. Chem. 281: 26170-26180 | Abstract
- Elbing, K., R.R. McCartney and M.C. Schmidt. 2006. "Purification and Characterization of the three Snf1-activating kinases of Saccharomyces cerevisiae" Biochemical Journal 393: 797-805 | Abstract
- Ptacek J et al., 2005. "Global analysis of protein phosphorylation in yeast" Nature 438: 679-84. | Abstract
- McCartney RR, Rubenstein EM, Schmidt MC. 2005. "Snf1 kinase complexes with different beta subunits display stress-dependent preferences for the three Snf1-activating kinases" Curr Genet. 47: 335-44 | Abstract
- Sutherland CM, Hawley SA, McCartney RR, Leech A, Stark MJ, Schmidt MC, Hardie DG. 2003. "Elm1p is one of three upstream kinases for the Saccharomyces cerevisiae SNF1 complex" Curr Biol. 13:1299-305. | Abstract
- Nath N, McCartney RR, Schmidt MC. 2003. "Yeast Pak1 kinase associates with and activates Snf1" Mol Cell Biol. 23:3909-17. | Abstract
- Nath N, McCartney RR, Schmidt MC. 2002 "Purification and characterization of Snf1 kinase complexes containing a defined Beta subunit composition" J Biol Chem. 277:50403-8. | Abstract
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