Research Topics
Genomes and Genes | Henrik G DohlmanSummaryAffiliation: University of North Carolina Country: USA Publications
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Publications
Regulation of cell signaling dynamics by the protein kinase-scaffold Ste5Nan Hao
Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Mol Cell 30:649-56. 2008..We propose that scaffold proteins serve to modulate the temporal and dose-response behavior of the MAP kinase...
G proteins and pheromone signalingHenrik G Dohlman
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
Annu Rev Physiol 64:129-52. 2002....
A scaffold makes the switchHenrik G Dohlman
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599 7260, USA
Sci Signal 1:pe46. 2008..New findings reveal that the graded-to-binary conversion can be turned on or off, depending on the location of the scaffold within the cell...- Pheromone signaling pathways in yeastHenrik G Dohlman
Department of Biochemistry and Biophysics, Mary Ellen Jones Building Room 430, University of North Carolina, Chapel Hill, NC 27599 7260, USA
Sci STKE 2006:cm6. 2006..This updated Connections Map in the Database of Cell Signaling includes several major revisions to this prototypical signal response pathway... - Genome-scale analysis reveals Sst2 as the principal regulator of mating pheromone signaling in the yeast Saccharomyces cerevisiaeScott A Chasse
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599 7260, USA
Eukaryot Cell 5:330-46. 2006..These findings suggest that Sst2 is the principal regulator of Gpa1-mediated signaling in vivo but that other proteins also contribute in distinct ways to pathway regulation... - Systematic analysis of essential genes reveals important regulators of G protein signalingSteven D Cappell
Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Mol Cell 38:746-57. 2010..These insights to the G protein signaling network reveal the essential genome as an untapped resource for identifying new components and regulators of signal transduction pathways... - Persistent activation by constitutive Ste7 promotes Kss1-mediated invasive growth but fails to support Fus3-dependent mating in yeastSeth Maleri
Department of Biochemistry and Biophysics, CB 7260, 512 ME Jones, University of North Carolina, Chapel Hill, NC 27599 7260, USA
Mol Cell Biol 24:9221-38. 2004..This scaffold-independent activation of Kss1 by constitutive Ste7 and the existence of mechanisms for pathway-specific promoter discrimination impose a unique developmental fate independently of any distinguishing external stimuli... - Combined computational and experimental analysis reveals mitogen-activated protein kinase-mediated feedback phosphorylation as a mechanism for signaling specificityNan Hao
Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Mol Biol Cell 23:3899-910. 2012..These findings reveal how feedback phosphorylation of a common pathway component can limit the activity of a competing MAP kinase through feedback phosphorylation of a common activator, and thereby promote signal fidelity... - Control of MAPK specificity by feedback phosphorylation of shared adaptor protein Ste50Nan Hao
Department of Biochemistry, University of North Carolina, Chapel Hill, North Carolina 27599 7260, USA
J Biol Chem 283:33798-802. 2008..Thus feedback regulation of a shared component can restrict the activity of a competing MAP kinase to ensure signal fidelity... - A systems-biology analysis of feedback inhibition in the Sho1 osmotic-stress-response pathwayNan Hao
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Curr Biol 17:659-67. 2007..For instance in yeast, the mitogen-activated protein (MAP) kinase Hog1 is activated and inactivated within minutes, even when the osmotic-stress stimulus is sustained... - The RACK1 ortholog Asc1 functions as a G-protein beta subunit coupled to glucose responsiveness in yeastCorinne E Zeller
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599, USA
J Biol Chem 282:25168-76. 2007..Our findings reveal the existence of an unusual Gbeta subunit, one having multiple functions within the cell in addition to serving as a signal transducer for cell surface receptors and intracellular effectors... - Pheromone-regulated sumoylation of transcription factors that mediate the invasive to mating developmental switch in yeastYuqi Wang
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599 7260, USA
J Biol Chem 281:1964-9. 2006..In the absence of sumoylation Tec1 is more rapidly degraded. We propose that pheromone-regulated sumoylation of Ste12 and Tec1 promotes a developmental switch from the invasive to the mating differentiation program... - G protein signaling in yeast: new components, new connections, new compartmentsJanna E Slessareva
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599-7260, USA
Science 314:1412-3. 2006..New tools available in yeast are beginning to uncover new pathway components and interactions and have revealed signaling in unexpected locations within the cell... - Activation of the phosphatidylinositol 3-kinase Vps34 by a G protein alpha subunit at the endosomeJanna E Slessareva
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Cell 126:191-203. 2006..These findings reveal two new components of the pheromone signaling pathway. More remarkably, these proteins appear to comprise a preformed effector-G beta subunit assembly and function at the endosome rather than at the plasma membrane... - Structure and function of Vps15 in the endosomal G protein signaling pathwayErin J Heenan
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599 7260, USA
Biochemistry 48:6390-401. 2009..These findings reveal that the Vps15 Gbeta-like domain serves as a scaffold to assemble Gpa1 and Atg14, whereas the kinase and intermediate domains are required for proper signaling at the endosome... - Coactivation of G protein signaling by cell-surface receptors and an intracellular exchange factorMichael J Lee
Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7365, USA
Curr Biol 18:211-5. 2008..Our data suggest that intracellular proteins function in cooperation with mating pheromones to amplify G protein signaling, thereby leading to full pathway activation... - Bistability, stochasticity, and oscillations in the mitogen-activated protein kinase cascadeXiao Wang
Department of Statistics and Operations Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7365, USA
Biophys J 90:1961-78. 2006..We demonstrate that the inclusion of protein turnover can lead to sustained oscillations of protein concentrations in the absence of feedback regulation. Thus, protein turnover can profoundly influence the output of a signaling pathway... - Selective regulation of MAP kinase signaling by an endomembrane phosphatidylinositol 4-kinaseSteven D Cappell
Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
J Biol Chem 286:14852-60. 2011..These findings reveal a new regulator of signaling specificity functioning at endomembranes rather than at the plasma membrane... - Cell cycle-dependent phosphorylation and ubiquitination of a G protein alpha subunitMatthew P Torres
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7260, USA
J Biol Chem 286:20208-16. 2011..These findings demonstrate that Gpa1 is dynamically regulated. More broadly, they reveal how G proteins can simultaneously regulate, and become regulated by, progression through the cell cycle... - Proper protein glycosylation promotes mitogen-activated protein kinase signal fidelityEvan C Lien
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Biochemistry 52:115-24. 2013..These findings reveal new components of the N-glycosylation machinery needed to ensure MAPK signaling fidelity... - Phosphorylation of the RGS protein Sst2 by the MAP kinase Fus3 and use of Sst2 as a model to analyze determinants of substrate sequence specificityStephen C Parnell
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill 27599 7260, USA
Biochemistry 44:8159-66. 2005..This analysis documents phosphorylation of Sst2 by Fus3 and demonstrates that the prevailing model for MAP kinase recognition is valid for a native substrate protein in vivo as well as for small synthetic peptides tested in vitro... - Pheromone signaling mechanisms in yeast: a prototypical sex machineYuqi Wang
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599-7260, USA
Science 306:1508-9. 2004.... - G Protein Mono-ubiquitination by the Rsp5 Ubiquitin LigaseMatthew P Torres
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599 7260, USA
J Biol Chem 284:8940-50. 2009.... - Functional reconstitution of an atypical G protein heterotrimer and regulator of G protein signaling protein (RGS1) from Arabidopsis thalianaJanice C Jones
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
J Biol Chem 286:13143-50. 2011..Thus, despite profound differences in the mechanisms of activation, the Arabidopsis G protein is readily inactivated by its cognate RGS protein and forms a stable, GDP-bound, heterotrimeric complex similar to that found in animals... - Yeast dynamically modify their environment to achieve better mating efficiencyMeng Jin
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA
Sci Signal 4:ra54. 2011..Thus, budding yeast dynamically remodel their environment to ensure productive responses to an external stimulus and avoid nonproductive cell-cell interactions... - Regulation of Ste7 ubiquitination by Ste11 phosphorylation and the Skp1-Cullin-F-box complexYuqi Wang
Department of Biochemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-2852, USA
J Biol Chem 278:22284-9. 2003..Our findings suggest that SCF promotes the ubiquitination and degradation of Ste7, thereby favoring the resumption of cell division cycling after pheromone-induced growth arrest... - Mathematical and computational analysis of adaptation via feedback inhibition in signal transduction pathwaysMarcelo Behar
Department of Physics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Biophys J 93:806-21. 2007..Finally, we present characteristic features for each form of feedback regulation that can aid in their identification... - Regulators of G protein signaling and transient activation of signaling: experimental and computational analysis reveals negative and positive feedback controls on G protein activityNan Hao
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-0812, USA
J Biol Chem 278:46506-15. 2003..We identified and quantitated these positive and negative feedback loops, which account for the transient response to external signals observed in vivo... - Differential regulation of G protein alpha subunit trafficking by mono- and polyubiquitinationYuqi Wang
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599 7260, USA
J Biol Chem 280:284-91. 2005..These data reveal a strong relationship between the extent of ubiquitination and trafficking of the G protein alpha subunit to its site of degradation... - Dominant-negative inhibition of pheromone receptor signaling by a single point mutation in the G protein alpha subunitYuh Lin Wu
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill 27599 7260, USA
J Biol Chem 279:35287-97. 2004..Dominant-negative mutants may be useful in matching specific receptors and their cognate G proteins and in determining mechanisms of G protein signaling specificity... - Site-specific monoubiquitination activates Ras by impeding GTPase-activating protein functionRachael Baker
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Nat Struct Mol Biol 20:46-52. 2013..These findings reveal a new mechanism by which Ras can trigger persistent signaling in the absence of receptor activation or an oncogenic mutation... - Differences in intradomain and interdomain motion confer distinct activation properties to structurally similar Gα proteinsJanice C Jones
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA
Proc Natl Acad Sci U S A 109:7275-9. 2012..Thus, structurally similar proteins can have distinct atomic motions that confer distinct activation mechanisms... - Identification of yeast pheromone pathway modulators by high-throughput agonist response profiling of a yeast gene knockout strain collectionScott A Chasse
Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, 27599-7260, USA
Methods Enzymol 389:399-409. 2004..This article describes a high-throughput method of analyzing a yeast gene deletion library for novel G-protein signaling modulators using a yeast pheromone pathway-specific reporter... - The yeast G protein alpha subunit Gpa1 transmits a signal through an RNA binding effector protein Scp160Ming Guo
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Mol Cell 12:517-24. 2003..We also show that signaling by activated Gpa1 requires direct coupling to an RNA binding protein Scp160. These findings suggest an additional role for Gpa1 and reveal Scp160 as a component of the mating response pathway in yeast... - Kinetic insulation as an effective mechanism for achieving pathway specificity in intracellular signaling networksMarcelo Behar
Department of Physics, University of North Carolina, Chapel Hill, NC 27599, USA
Proc Natl Acad Sci U S A 104:16146-51. 2007..Our results suggest that multilevel signaling cascades may have evolved to modulate the temporal profile of pathway activity so that stimulus information can be efficiently encoded and transmitted while ensuring signal specificity... - Pheromone-dependent ubiquitination of the mitogen-activated protein kinase kinase Ste7Yuqi Wang
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599 2852, USA
J Biol Chem 277:15766-72. 2002..These findings reveal a mechanism by which pheromone-triggered ubiquitination of Ste7 can modulate the pheromone response in vivo... - The crystal structure of a self-activating G protein alpha subunit reveals its distinct mechanism of signal initiationJanice C Jones
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA
Sci Signal 4:ra8. 2011..These findings reveal the structural basis for a mechanism for G protein activation in Arabidopsis that is distinct from the well-established mechanism found in animals... - Signal activation and inactivation by the Gα helical domain: a long-neglected partner in G protein signalingHenrik G Dohlman
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Sci Signal 5:re2. 2012..Historically most attention has focused on the Ras-like domain, but emerging evidence reveals that the helical domain is an active participant in G protein signaling... - RGS proteins the early daysHenrik G Dohlman
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599 7260, USA
Prog Mol Biol Transl Sci 86:1-14. 2009.... - Illuminating Gbeta5 signalingCorinne E Zeller
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, 116 Manning Dr, CB 7260, Chapel Hill, NC 27599, USA
Mol Pharmacol 72:810-1. 2007..The approach used here provides a new strategy to elucidate the spatial and temporal properties of G proteins, including a growing number of atypical Gbetagamma pairings... - Diminishing returnsHenrik G Dohlman
Department of Biochemistry and Biophysics, University of North Carolina, Campus Box 7260, Chapel Hill, North Carolina 27599-2852, USA
Nature 418:591. 2002 - Similarities between UDP-glucose and adenine nucleotide release in yeast: involvement of the secretory pathwayCharles R Esther
Division of Pediatric Pulmonology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
Biochemistry 47:9269-78. 2008..These studies demonstrate the involvement of the secretory pathway in nucleotide and nucleotide sugar efflux in yeast and offer a powerful model system for further investigation... - MAPK kinase kinases (MKKKs) as a target class for small-molecule inhibition to modulate signaling networks and gene expressionGary L Johnson
Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, NC 27599 7365, USA
Curr Opin Chem Biol 9:325-31. 2005.... - Regulation of G protein and mitogen-activated protein kinase signaling by ubiquitination: insights from model organismsYuqi Wang
Department of Biology, Saint Louis University, 128 Macelwane Hall, 3507 Laclede Ave, St Louis, MO 63103, USA
Circ Res 99:1305-14. 2006..Similar mechanisms uncovered in other model systems are also briefly discussed to illustrate the importance and universality of signaling regulation by ubiquitination... - Regulation of stress response signaling by the N-terminal dishevelled/EGL-10/pleckstrin domain of Sst2, a regulator of G protein signaling in Saccharomyces cerevisiaeScott A Burchett
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06536, USA
J Biol Chem 277:22156-67. 2002..These findings indicate that Vps36 and Sst2 have opposite and opposing effects on the pheromone and stress response pathways, with Vps36 acting downstream of the G protein and independently of Sst2 RGS activity... - Mathematical modeling of RGS and G-protein regulation in yeastNecmettin Yildirim
Department of Mathematics, University of North Carolina at Chapel Hill, 27599-3250, USA
Methods Enzymol 389:383-98. 2004..It also illustrates that a complete understanding of signaling pathways requires an investigation of their time-dependent behavior... - Direct identification of a G protein ubiquitination site by mass spectrometryLouis A Marotti
Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, Connecticut 06536, USA
Biochemistry 41:5067-74. 2002..These findings indicate that the alpha-helical domain may serve to regulate the turnover of Gpa1... - Dose-to-duration encoding and signaling beyond saturation in intracellular signaling networksMarcelo Behar
Department of Physics, University of North Carolina Chapel Hill, Chapel Hill, North Carolina, United States of America
PLoS Comput Biol 4:e1000197. 2008.... - Purification of RGS protein, Sst2, from Saccharomyces cerevisiae and Escherichia coliTiffany Runyan Garrison
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06536, USA
Methods Enzymol 344:632-47. 2002 - Identification of allosteric peptide agonists of CXCR4Aristidis Sachpatzidis
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
J Biol Chem 278:896-907. 2003..111. These results suggest that alternative agonist-binding sites are present on CXCR4 that could be screened to develop molecules for therapeutic use... - Analysis of RGS proteins in Saccharomyces cerevisiaeGinger A Hoffman
Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut 06536, USA
Methods Enzymol 344:617-31. 2002 - DEP-domain-mediated regulation of GPCR signaling responsesDaniel R Ballon
Department of Molecular and Cell Biology, Division of Biochemistry and Molecular Biology, University of California, Berkeley, CA 94720, USA
Cell 126:1079-93. 2006..DEP-domain-mediated targeting of effectors and regulators to specific GPCRs provides a means to dictate the nature, duration, and specificity of the response...