Research Topics
| HENRIK DOHLMANSummaryAffiliation: University of North Carolina Country: USA Publications
Research Grants
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Detail Information
Publications
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...
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...- 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... 
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...- 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.... - 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.... - 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... - 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... - 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... - 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... - 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... - 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... - 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... - 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... - 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... - 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.... - 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... - 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... - 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.... - 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... - 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... - 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... - 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... - 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... - 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... - 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 - 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... - 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... - 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... - 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... - 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... - 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... - 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... - 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... - 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
Research Grants
- REGULATORS OF G PROTEIN SIGNALING IN YEASTHENRIK DOHLMAN; Fiscal Year: 2007..Delineating such new pathways is the principal objective of this proposal. ..
- G Protein signaling at the endosomeHENRIK DOHLMAN; Fiscal Year: 2007..abstract_text> ..
- G Protein signaling at the endosomeHenrik G Dohlman; Fiscal Year: 2010....
- Modeling Feedback Regulation of Cell SignalingHenrik G Dohlman; Fiscal Year: 2010..The broader objective is to understand the role of spatial and temporal information in cell signaling, and eventually predict what drug treatments will be most effective in combating human diseases. ..
- REGULATORS OF G PROTEIN SIGNALING IN YEASTHenrik G Dohlman; Fiscal Year: 2010..Delineating such new pathways is the principal objective of this proposal. ..
- G Protein signaling at the endosomeHENRIK DOHLMAN; Fiscal Year: 2007....
- Gordon Conference on "Phosphorylation and G Protein Signaling Networks"HENRIK DOHLMAN; Fiscal Year: 2007..To emphasize this goal, 8 poster presentations that complement the themes of the meeting will be selected for short oral presentations during the main sessions. ..
- Modeling Feedback Regulation of Cell SignalingHENRIK DOHLMAN; Fiscal Year: 2007..An integrated computational and experimental analysis of the pheromone regulation in yeast will eventually lead to improved predictive models of signaling events in more complex organisms including humans. ..
- REGULATION OF SIGNALING BY G PROTEIN-BINDING PROTEINSHENRIK DOHLMAN; Fiscal Year: 2004..The molecular and cellular consequences of each modification will be evaluated using standard assays of RGS and G protein function. ..
- REGULATORS OF G PROTEIN SIGNALING IN YEASTHENRIK DOHLMAN; Fiscal Year: 2006..These experiments will reveal how cell signaling is regulated through feedback regulation of an effector kinase, initially in yeast and eventually in mammalian cells. ..
- Modeling Feedback Regulation of Cell SignalingHenrik G Dohlman; Fiscal Year: 2010..The broader objective is to understand the role of spatial and temporal information in cell signaling, and eventually predict what drug treatments will be most effective in combating human diseases. ..