Research Interests The ability to respond to changes in the extracellular environment is fundamental to all cells. The growth of mammalian cells is controlled in part by extracellular cytokines which bind to integral membrane receptors that in turn regulate the activity of intracellular protein kinases. In Saccharomyces cerevisiae, the response to changes in extracellular glucose concentration shares many similarities with mammalian cytokine signaling pathways. The glucose sensor proteins encoded by SNF3 and RGT2 are integral membrane proteins that bind extracellular glucose and initiate a signaling pathway that ultimately results in changes in gene expression. The Snf1 serine/threonine protein kinase plays an essential role in signaling glucose limitation, however the mechanism by which the glucose sensors regulate the activity of the Snf1 kinase has yet to be elucidated. The mammalian homologue of Snf1 is the AMP-activated protein kinase, an important therapeutic target for type II diabetes. Our recent studies have focused on the Snf1 kinase of yeast. 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 a distinct upstream kinase. Recently we have shown that affinity purified Snf1 kinase can be activated in vitro by the upstream kinase. Experiments designed to identify and characterize the Snf1-activating kinase are underway. 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. 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.   Selected Publications Rubenstein EM, McCartney RR, Zhang C, Shokat KM, Shirra MK, Arndt KM, Schmidt MC. Access denied: Snf1 activation loop phosphorylation is controlled by availability of the phosphorylated threonine 210 to the PP1 phosphatase. J Biol Chem. 2008 Jan 4;283(1):222-30. Epub 2007 Nov 8. Rubenstein EM, Schmidt MC. Mechanisms regulating the protein kinases of Saccharomyces cerevisiae. Eukaryot Cell. 2007 Apr;6(4):571-83. Epub 2007 Mar 2. Review. No abstract available. Elbing K, McCartney RR, Schmidt MC. Purification and characterization of the three Snf1-activating kinases of Saccharomyces cerevisiae. Biochem J. 2006 Feb 1;393(Pt 3):797-805. Rubenstein EM, McCartney RR, Schmidt MC. Regulatory domains of Snf1-activating kinases determine pathway specificity. Eukaryot Cell. 2006 Apr;5(4):620-7. Ptacek J, Devgan G, Michaud G, Zhu H, Zhu X, Fasolo J, Guo H, Jona G, Breitkreutz A, Sopko R, McCartney RR, Schmidt MC, Rachidi N, Lee SJ, Mah AS, Meng L, Stark MJ, Stern DF, De Virgilio C, Tyers M, Andrews B, Gerstein M, Schweitzer B, Predki PF, Snyder M. Global analysis of protein phosphorylation in yeast. Nature. 2005 Dec 1;438(7068):679-84. Complete Publication Listing   Grant Support NIH/NIGMS R01 GM46443-16 Mechanism of glucose signal transduction in yeast. Principal Investigator   Other Links MMG Faculty Webpage Schmidt Home Page Interdisciplinary Biomed. Grad. Program University of Pittsburgh

Martin C Schmidt, Ph.D. Associate Professor Office:  BST W1247 Lab:BST W1212 / BST W1210 Phone:412-648-9243 Fax: 412-624-1401 mcs2@pitt.edu   Academic Affiliations Associate Professor Department of Microbiology and Molecular Genetics University of Pittsburgh School of Medicine Member, Pittsburgh Cancer Institute University of Pittsburgh School of Medicine Member Molecular Virology and Microbiology Program University of Pittsburgh School of Medicine Member Biochemistry and Molecular Genetics Program University of Pittsburgh School of Medicine   Education 1979 B.A. Zoology University of Vermont Burlington, VT 1985 Ph.D. Biochemistry University of California/Berkley 1986 - 1990 Postdoc Molecular Biology University of California/Los Angeles   Lab Personnel Postdoctoral Fellow: Karin Elbing Graduate Student: Eric (VJ) Rubenstein Undergrad Researcher: Natalie Pappas Lab Manager: Rhonda McCartney