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Martin C. Schmidt, PhD

Dr. Martin Schmidt


521 Bridgeside Point II
450 Technology Drive


PhD, University of California, Berkeley

BS, University of Vermont

Academic Affiliation(s)

Professor, Department of Microbiology and Molecular Genetics

Member,  Molecular Genetics and Developmental Biology Graduate Program

Member, Molecular Virology and Microbiology Program


My lab studies 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 now know 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. The yeast PP1 phosphatase is responsible for the dephosphorylation of Snf1 in response to changes in carbon source. We have shown that the PP1 phosphatase is active in low glucose toward most substrates. However, the Snf1 kinase becomes resistant to dephosphorylation. These data indicate that the active Snf1 kinase can adopt a phosphatase resistant structure. The phosphatase resistant structure is stabilized in vitro by binding low energy adenylate ligands such as AMP and ADP. In this way, the Snf1 kinase is a direct sensor of the cell's energy status with low energy adenylate ligands stabilizing the active form of Snf1 which then promotes ATP synthesis and conservation. 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.

Lab Personnel

Rhonda McCartney, Lab Manager


Zhang Y, McCartney R. R, Chandrashekarappa D. G, Mangat S, and Schmidt M. C. Reg1 protein regulates phosphorylation of all three Snf1 isoforms but preferentially associates with the Gal83 isoform. Eukaryot Cell. 10: 1628-1636. |  View Abstract

Mayer F. V, Heath R, Underwood E, Sanders M. J, Carmena D, McCartney R. R, Leiper F. C, Xiao B, Jing C, Walker P. A, Haire L. F, Ogrodowicz R, Martin S. R, Schmidt M. C, Gamblin S. J, and Carling D. ADP regulates SNF1, the Saccharomyces cerevisiae homolog of AMP-activated protein kinase. Cell Metab. 14: 707-714. |  View Abstract

Chandrashekarappa D. G, McCartney R. R, and Schmidt M. C. Subunit and domain requirements for adenylate-mediated protection of Snf1 kinase activation loop from dephosphorylation. J Biol Chem. 286: 44532-44541. |  View Abstract

Tabba S, Mangat S, McCartney R, Schmidt M. C. PP1 phosphatase-binding motif in Reg1 protein of Saccharomyces cerevisiae is required for interaction with both the PP1 phosphatase Glc7 and the Snf1 protein kinase. Cell Signal. 22: 1013-1021. |  View Abstract

Mangat S, Chandrashekarappa D, McCartney R. R, Elbing K, Schmidt M. C. Differential roles of the glycogen-binding domains of beta subunits in regulation of the Snf1 kinase complex. Eukaryot Cell. 9: 173-183. |  View Abstract

Shirra M. K, McCartney R. R, Zhang C, Shokat K. M, Schmidt M. C, and Arndt K. M. A chemical genomics study identifies Snf1 as a repressor of GCN4 translation. J Biol Chem. 283: 35889-35898. |  View Abstract

Rubenstein E. M, McCartney R. R, Zhang C, Shokat K. M, Shirra M. K, Arndt K. M, and Schmidt M. C. 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. |  View Abstract