Henrik Dohlman, PhD

• Dohlman Lab Website
• Publication List

RESEARCH INTERESTS:

Regulators of G Protein Signaling

In my laboratory, we study the molecular mechanisms of desensitization.  Our primary focus is the regulation of G proteins, which transmit signals from cell surface receptors to intracellular targets.  G protein-coupled receptors bind to neurotransmitters (e.g. adrenaline), peptide hormones (e.g. opiods), odors, taste and light.  Genetic defects in these pathways can cause a variety of developmental and metabolic disorders, including cancer, obesity, narcolepsy, drug addiction, and resistance to HIV infection. 

G proteins are highly conserved and are even found in the simplest eukaryotes, such as the yeast Saccharomyces cerevisiae.  We are currently using genetic screens to identify mutants with altered signaling and desensitization properties in yeast.  Such mutants are then characterized biochemically, both in yeast and in humans (using homologous components).  This approach has led to the discovery of a new family of desensitization factors, called RGS proteins (Regulator of G protein signaling).  RGS proteins promote G protein inactivation through their ability to accelerate their GTPase activity.  Presently we are using mass spectrometry to determine how RGS proteins are themselves regulated through post-translational modifications.  In addition we are using genetic screens to identify new desensitization factors and their homologues in humans.

RECENT PUBLICATIONS:

Hao N, Nayak S, Behar M, Shanks RH, Nagiec MJ, Errede B, Hasty J, Elston TC, Dohlman HG. Regulation of cell signaling dynamics by the protein kinase-scaffold Ste5. Mol Cell. 2008 Jun 6;30(5):649-56.

Lee MJ, Dohlman HG. Coactivation of G protein signaling by cell-surface receptors and an intracellular exchange factor. Curr Biol. 2008 Feb 12;18(3):211-5.

Behar M, Dohlman HG, Elston TC. Kinetic insulation as an effective mechanism for achieving pathway specificity in intracellular signaling networks. Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16146-51.

Zeller CE, Dohlman HG. Illuminating Gbeta5 signaling. Mol Pharmacol. 2007 Oct;72(4):810-1.

Zeller CE, Parnell SC, Dohlman HG. The RACK1 ortholog Asc1 functions as a G-protein beta subunit coupled to glucose responsiveness in yeast. J Biol Chem. 2007 Aug 24;282(34):25168-76.

Behar M, Hao N, Dohlman HG, Elston TC. Mathematical and computational analysis of adaptation via feedback inhibition in signal transduction pathways. Biophys J. 2007 Aug 1;93(3):806-21.

Hao N, Behar M, Parnell SC, Torres MP, Borchers CH, Elston TC, Dohlman HG. A systems-biology analysis of feedback inhibition in the Sho1 osmotic-stress-response pathway. Curr Biol. 2007 Apr 17;17(8):659-67.

Wang Y, Dohlman HG. Regulation of G protein and mitogen-activated protein kinase signaling by ubiquitination: insights from model organisms. Circ Res. 2006 Dec 8;99(12):1305-14. Review.

Dohlman HG, Slessareva JE. Pheromone signaling pathways in yeast. Sci STKE. 2006 Dec 5;2006(364):cm6. Review.

Slessareva JE, Dohlman HG. G protein signaling in yeast: new components, new connections, new compartments. Science. 2006 Dec 1;314(5804):1412-3.

Ballon DR, Flanary PL, Gladue DP, Konopka JB, Dohlman HG, Thorner J. DEP-domain-mediated regulation of GPCR signaling responses. Cell. 2006 Sep 22;126(6):1079-93.

Slessareva JE, Routt SM, Temple B, Bankaitis VA, Dohlman HG. Activation of the phosphatidylinositol 3-kinase Vps34 by a G protein alpha subunit at the endosome. Cell. 2006 Jul 14;126(1):191-203.

Chasse SA, Flanary P, Parnell SC, Hao N, Cha JY, Siderovski DP, Dohlman HG. Genome-scale analysis reveals Sst2 as the principal regulator of mating pheromone signaling in the yeast Saccharomyces cerevisiae. Eukaryot Cell. 2006 Feb;5(2):330-46.

Wang X, Hao N, Dohlman HG, Elston TC. Bistability, stochasticity, and oscillations in the mitogen-activated protein kinase cascade. Biophys J. 2006 Mar 15;90(6):1961-78.

Wang Y, Dohlman HG. Pheromone-regulated sumoylation of transcription factors that mediate the invasive to mating developmental switch in yeast. J Biol Chem. 2006 Jan 27;281(4):1964-9.

Parnell SC, Marotti LA Jr, Kiang L, Torres MP, Borchers CH, Dohlman HG. Phosphorylation of the RGS protein Sst2 by the MAP kinase Fus3 and use of Sst2 as a model to analyze determinants of substrate sequence specificity. Biochemistry. 2005 Jun 7;44(22):8159-66.

Johnson GL, Dohlman HG, Graves LM. MAPK kinase kinases (MKKKs) as a target class for small-molecule inhibition to modulate signaling networks and gene expression. Curr Opin Chem Biol. 2005 Jun;9(3):325-31. Review.