Dept. Microbiology and Molecular Genetics
University of Pittsburgh School of Medicine
Pittsburgh, PA 15261
(412) 648-9243 Office
(412) 648-9380 Lab
mcs2@pitt.edu
Class
Graduate Program
Graduate Program
|
Martin C. Schmidt, Ph.D. Dept. Microbiology and Molecular Genetics University of Pittsburgh School of Medicine Pittsburgh, PA 15261 (412) 648-9243 Office (412) 648-9380 Lab mcs2@pitt.edu |
|
| Biocomputing Class |
Biochemistry and
Molecular Genetics Graduate Program |
Interdisciplinary
Biomedical Graduate Program |
Research Interests
|
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. |
Recent Publications:
| 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. Biological Chemistry 283: 222-230. |
Download PDF file |
| Rubenstein, E.M. and M.C. Schmidt (2007) "Mechanisms regulating the protein kinases of Saccharomyces cerevisiae" Eukaryotic Cell 6: 571-583. |
Download PDF file |
| 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. Biological Chemistry 281:26170-26180. |
Abstract |
|
Rubenstein, E.M., R.R. McCartney and M.C. Schmidt (2006) "Regulatory Domains of the Snf1-Activating Kinases Determine Pathway Specificity" Eukaryotic Cell 5: 620-627. |
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: 679-684. |
Abstract |
| McCartney, R.R., E.M. Rubenstein and M.C. Schmidt (2005) "Snf1 kinase complexes with different beta subunits display stress-dependent preferences for the three Snf1-activating kinases" Current Genetics 47: 335-344. |
Abstract |
| Sutherland, C. M., S.A. Hawley, R.R. McCartney, A. Leech,
M.J.R. Stark, M.C. Schmidt, and D. G. Hardie (2003) "Elm1p Is One of Three Upstream Kinases for the Saccharomyces cerevisiae SNF1 complex" Current Biology 13:1299-1305. |
Abstract |
| Nath, N., R.R. McCartney and M. C. Schmidt (2003) "Yeast PAK1 Kinase Associates with and Activates Snf1" Molecular and Cellular Biology 23: 3909-3917. | Abstract |
| A. Leech, N. Nath, R.R. McCartney, and M. C. Schmidt (2003) "Isolation of mutations in the catalytic domain of the Snf1 kinase that render its activity independent of the Snf4 subunit" Eukaryotic Cell 2:265-273. |
Abstract |
| Nath, N., R. R. McCartney and M. C. Schmidt (2002) "Purification and characterization of Snf1 kinase complexes containing a defined beta subunit composition" J. Biological Chemistry 277:50403-50408. |
Abstract |
McCartney, R. R. and Schmidt, M. C. (2001) |
Abstract |
Schmidt, M. C. and R.R. McCartney (2000) |
Abstract |
| Schmidt, M. C., R.R. McCartney, X. Zhang, T.S. Tillman, H. Solimeo, S. Wolfl, C.
Almonte, & S. Watkins. (1999) "Std1 and Mth1 proteins interact with the glucose sensors to control glucose-regulated gene expression in Saccharomyces cerevisiae". Molecular and Cellular Biology 19:4561-4571. |
Abstract |
| Quinn, J., A.M. Fryberg, R.W. Ganster, M.C. Schmidt, and C.L. Peterson (1996) "DNA Binding properties of the yeast SWI/SNF complex." Nature, 379:844-847. |
Abstract |
 Rhonda McCartney rorhonda@hotmail.com |
 Karin Elbing, Ph.D. karin_elbing@yahoo.se |
 VJ Rubenstein yajeev80@yahoo.com |
 Daksha Chandrashekarappa dakshayinichethan@gmail.com |
 Annie Bedison bedisonma@upmc.edu |
 Pavol Ganzor pavol.genzor@email.stvincent.edu |