Professor of Biology
Professor of Biology
B.S., North Carolina State;
Ph.D., Yale University
Member of: Institute of Molecular Biology
Office: Streisinger Hall Room 245C
Lab: Streisinger Hall Room 245
Intracellular signal transduction pathways provide a means for eukaryotic cells to respond to external stimuli and mount an appropriate physiological response. The pathways can quite sophisticated, containing branch points, and hence the physiological response can be likewise sophisticated. Even in the best-studied cases, how pathway activity is regulated and how it achieves a full spectrum of physiological responses is not understood. Moreover, the gaps in our understanding are compounded by the observations made in recent years that signal transduction pathways that operate in the same cells often share components. This realization raises the question as to how pathway integrity is maintained when a cell is responding to a particular environmental cue.
Illustrations of all these issues occur in signal transduction pathways found the yeast Saccharomyces cerevisiae. The relatively straight forward genetics and molecular biology of this particular organism should facilitate the dissection of these complex issues, and the lessons learned will likely have application in other organisms as well. There are two broad goals for the work being carried out. The first is to understand how distinct environmental cues can activate strikingly similar signal transduction pathways but nonetheless lead to distinct physiological outputs. What mechanisms ensure pathway integrity and limit cross-talk? What is the molecular nature of branches that connect signal transduction pathways to the basic cell biological machinery and thereby control cellular morphogenesis? The second broad goal is to focus on one particular signal transduction pathway, the pheromone response pathway, and gain insight into how this pathway regulates progression through the cell cycle.
Localization of Bud4p, a protein required for the axial budding pattern. Bud4p was fused to green fluorescence protein (GFP) and visualized by virtue of the intrinsic fluorescence of GFP. Although the budding pattern of yeast cells changes when they are shifted from glucose rich to glucose limiting conditions, the localization of Bud4p does not change.
Sprague GF Jr, Winans SC.Eukaryotes learn how to count: quorum sensing by yeast. Genes Dev. 2006 May 1;20(9):1045-9.
Sprague, G.F., Jr. Differentiation: mating and filamentation. In: Landmarks of Yeast Biology. Cold Spring Harbor Laboratory Press pp141-155 (2006).Devit M, Cullen PJ, Branson M, Sprague GF Jr, Fields S. Forcing interatctions as a genetic screen to identify proteins that exert a defined activity. Genome Res . 2005 Apr;15(4):560-5.
Sprague, G.F. Three-pronged genomic analysis reveals yeast cell-type regulation circuitry. Proc Natl Acad Sciences 2005 Jan 25;102(4):959-60. Epub 2005 Jan 18.
Sprague, G.F., Cullen, P.J. and Goehring, A.S. Yeast signal transduction: regulation and interface with cell biology. Advances in Systems Biology (Opresko, L.K., Gephart, J.M. and Mann, M.B., Editors) Northwest Symposium on Systems Biology, PNL Press, pp 91-105 (2004)
Cullen, P.J., W. Sabbagh, Jr., E. Graham, M.M Irick, E.K. van Olden, C. Neal, J. Delrow, L. Bardwell, and G.F. Sprague Jr. (2004) A signaling mucin at the head of the Cdc42- and MAPK-dependent filamentous growth pathway in yeast. Genes Dev 18:1695-708.
Sprague, G.F. Jr., P.J. Cullen, and A.S. Goehring. (2004) Yeast signal transduction: Regulation and interface with cell biology. In: Advances in Experimental Medicine and Biology, V547, Advances in Systems Biology, Kluwer Academic/Plenum Publishers, pp91-105.
Keniry, M.E., H.A. Kemp, D.M. Rivers, and G.F. Sprague Jr. (2004) The identification of Pc11-interacting proteins that genetically interact with Cla4 may indicate a link between G1 progression and mitotic exit. Genetics 166:1177-86.
Goehring A.S., D.M. Rivers, and G.F. Sprague Jr. (2003) Attachment of the ubiquitin-related protein Urm1p to the antioxidant protein Ahp1p. Eukaryot Cell 2:930-6.
Goehring, A.S., D.M. Rivers, and G.F. Sprague, Jr. (2003) Urmylation: A Ubiquitin-like Pathway that Functions during Invasive Growth and Budding in Yeast. Mol Biol Cell 14:4329-41.
Rivers D.M. and G.F. Sprague, Jr. (2003) Autocrine activation of the pheromone response pathway in matalpha2(-) cells is attenuated by SST2- and ASG7-dependent mechanisms. Mol Genet Genomics 270:225-33.
Goehring A.S., D.M. Rivers, and G.F. Sprague, Jr. (2003) Attachment of the ubiquitin-related protein Urm1p to the antioxidant protein Ahp1p. Eukaryot Cell 2:930-6.
Goehring, A.S., D.A. Mitchell, A.H.Y. Tong, M. Keniry, C. Boone, and G.F. Sprague, Jr. (2003) Synthetic lethal analysis implicates Ste20p, a p21-activated protein kinase, in polarisome activation. Mol Biol Cell 14:1501-16.
Keniry, M.E. and G.F. Sprague, Jr. (2003) Identification of p-21 activated kinase specificity determinants in budding yeast: a single amino acid substitution imparts Ste20 specificity to Cla4. Mol Cell Biol 23:1569-80.
Kemp, H.A. and Sprague, G.F., Jr. (2003) Far3 and five interacting proteins are required to prevent premature recovery from pheromone arrest in the budding yeast S. cerevisiae. Mol Cell Biol 23:1750-63.
Cullen, P. J. and G.F. Sprague, Jr. (2002) The roles of bud-site-selection proteins during haploid invasive growth in yeast. Mol Biol Cell 13:2990-3004.
Cullen, P.J. and G.F. Sprague, Jr. (2002) The Glc7p-interacting protein Bud14p attenuates polarized growth, pheromone response, and filamentous growth in Saccharomyces cerevisiae. Eukaryotic Cell 1:884-94.
Smith, G.R., S.A. Givan, P. Cullen, and G.F. Sprague, Jr. (2002) GTPase-activating proteins for Cdc 42. Eukaryotic Cell 1:469-80.
Mitchell D.A. and G.F. Sprague Jr. (2001) The phosphotyrosyl phosphatase activator, Ncs1p (Rrd1p), functions with Cla4p to regulate the G(2)/M transition in Saccharomyces cerevisiae. Mol Cell Biol. 21:488-500.
Cullen, P.J. and G.F. Sprague, Jr. (2000) Glucose depletion causes haploid invasive growth in yeast. PNAS 97:13619-24.
Cullen, P.J., J. Schultz, J. Horecka, B.J. Stevenson, Y. Jigami, and G.F. Sprague, Jr. (2000) Defects in protein glycosylation cause SHO1-dependent activation of a STE12 signaling pathway in yeast. Genetics 155:1005-18.
Horecka, J. and G.F. Sprague, Jr. (2000) Use of imidazoleglycerolphosphate dehydratase (His3) as a reporter in yeast. Methods in Enzymology 326:107-19.
Sprague, G.F., Jr.(1998) Control of MAP kinase signaling specificity or how not to go HOG wild. Genes & Dev. 12:2817-20.
Edwards, M.C., N. Liegeois, J. Horecka, R.A. DePinho, G.F. Sprague, Jr., M. Tyers, and S.J. Elledge. (1997) Human CPR (Cell cycle Progession Restoration) genes impart a Far-phenotype on yeast cells. Genetics 147:1063-76.
Sprague, G.F., Jr. and J. Printen. (1997) Two-hybrid analysis of protein-protein interactions in the yeast pheromone response pathway. In: The YeastTwo-hybrid System (P. L. Bartel and S. Fields, editors), Oxford University Press, pp 173-82.
Givan, S.A. And G.F. Sprague, Jr. (1997) The ankyrin repeat-containing protein Akr1p is required for the endocytosis of yeast pheromone receptors. Mol. Biol. Cell 8:1317-27.
Horecka, J. and G.F. Sprague, Jr. (1996) Identification and characterization of FAR3, a gene required for pheromone-mediated G1 arrest in Saccharomyces cerevisiae. Genetics 144:905-21.
Yashar, B., K. Irie, J.A. Printen, B.J. Stevenson, G.F. Sprague, Jr., K. Matsumoto, and B. Errede. (1995) Yeast MEK-dependent signal transduction: Response thresholds and parameters affecting fidelity. Mol Cell Biol. 15:6545-53.
Stevenson, B.J., B. Ferguson, C. De Virgilio, E.Bi, J.R. Pringle, G. Ammerer, and G.F. Sprague, Jr. (1995) Mutation of RGA1, which encodes a putative GAP for the polarity-establishment protein Cdc42p, activates the pheromone response pathway in the yeast Saccharomyces cerevisiae. Genes & Dev. 9:2949-63.
Printen, JA, and G.F. Sprague, Jr. (1994) Protein-protein interactions in the yeast pheromone response pathway: Ste5p interacts with all members of the MAP kinase cascade. Genetics 138: 609-19.
Bruhn, L. and G.F. Sprague, Jr. (1994) MCM1 point mutants deficient in expression of a-specific genes: Residues important for interaction with a1. Mol Cell Biol. 14:2534-44.
Davis, N.G., J.L. Horecka, and G.F. Sprague, Jr. (1993) Cis- and trans-acting functions required for endocytosis of yeast pheromone receptors. J Cell Biol. 122:53-65.
Stevenson, B.J., N. Rhodes, B. Errede, and G.F. Sprague, Jr. (1992) Constitutive mutants of the protein kinase STE11 activate the yeast pheromone response pathway in the absence of the G protein. Genes & Dev. 6:1293-304.
Bruhn, L., J.J. Hwang-Shum, and G.F. Sprague, Jr. (1992) The N-terminal 96 residues of MCM1, a regulator of cell type-specific genes in Saccharomyces cerevisiae, are sufficient for DNA binding, transcription activation, and interaction with a1. Mol Cell Biol. 12:3563-72.