Department of Pharmacology


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Heidi E. Hamm, Ph.D.

Professor of Ophthalmology and Visual Sciences
Professor of Pharmacology
Professor of Orthopaedic Surgery and Rehabilitation
Aileen M. Lange and Annie Mary Lyle Chair in Cardiovascular Research
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(615) 343-9536
442 RRB (6600)
Nashville, TN 37232-6600


Postdoc Fellow, University of Wisconsin - Madison
Ph.D., University of Texas, Austin
B.A., Atlantic Union College

Research Keywords

Signal transduction, structure and regulation of G-protein signaling, neuromodulation, exocytosis, vascular biology, networks of signaling pathways

Research Description

My work is focused on understanding the molecular basis of signaling mechanisms mediated by G proteins, which are switch proteins. G proteins are normally inactive, but a receptor that has received a specific signal can activate G proteins, leading to changes in the activity of enzymes that produce second messengers such as cyclic AMP and calcium.

The resulting changes in cellular activity underlie a large number of physiological processes. G protein-mediated signalling cascades are key regulators of many physiological processes, including processes of development, differentiation, and regulation of cell division. In the brain, many key neurotransmitters and neuromodulators mediate a myriad of functions by activation of such G protein cascades.

The research in my laboratory is aimed at understanding how G proteins become activated by receptors, how they in turn activate effector enzymes, and how they turn off. We determined the sites of interaction between proteins using a method of decomposing the proteins into small synthetic peptides and determining which peptides blocked interaction sites (Hamm et al., 1988; Rarick et al., 1992; Artemyev et al., 1993; Arshavsky et al., 1994). To understand the process more fully, we determined the atomic structure of the proteins in collaboration with the group of Paul Sigler. We used X-ray crystallography to solve the three-dimensional structures of G proteins in their inactive (GDP bound, (Lambright et al., 1994) and activated (GTPbgS-bound) forms (Noel et al., 1993). We caught a glimpse of the self-inactivating process in another crystal form, the transition state analog, Ga.GDP.AlF4- (Sondek et al., 1994). More recently, the structures of the bg subunit (Sondek et al., 1996) and the heterotrimeric G protein (Lambright et al., 1996) were solved. These high-resolution structural studies allowed us to postulate specific hypotheses regarding mechanisms of receptor:G protein interaction and activation, G protein subunit association-dissociation and effector activation.


Preininger, AM, Meiler, J, Hamm, HE. Conformational Flexibility and Structural Dynamics in GPCR-Mediated G Protein Activation: A Perspective. J Mol Biol, 2013 PMID: 23602809

Hamm, HE, Kaya, AI, Gilbert, JA, Preininger, AM. Linking receptor activation to changes in Sw I and II of Galpha proteins. J Struct Biol, 2013 PMID: 23466875

Li, X, Roszko, I, Sepich, DS, Ni, M, Hamm, HE, Marlow, FL, Solnica-Krezel, L. Gpr125 modulates Dishevelled distribution and planar cell polarity signaling. Development, 140(14), 3028-39, 2013 PMCID: PMC3699285

Duvernay, MT, Young, S, Gailani, D, Schoenecker, J, Hamm, HE. Protease-activated Receptor (PAR) 1 and PAR4 Differentially Regulate Factor V Expression from Human Platelets. Mol Pharmacol, 2013 PMCID: PMC3608438

Natarajan, C, Hata, AN, Hamm, HE, Zent, R, Breyer, RM. Extracellular Loop II Modulates GTP Sensitivity of the Prostaglandin EP3 Receptor. Mol Pharmacol, 83(1), 206-16, 2013 PMCID: PMC3533480

Young, SE, Duvernay, MT, Schulte, ML, Lindsley, CW, Hamm, HE. Synthesis of indole derived protease-activated receptor 4 antagonists and characterization in human platelets. PLoS One, 8(6), e65528, 2013

Thaker, TM, Kaya, AI, Preininger, AM, Hamm, HE, Iverson, TM. Allosteric mechanisms of G protein-Coupled Receptor signaling: a structural perspective. Methods Mol Biol, 796, 133-74, 2012 PMID: 22052489

Wells, CA, Zurawski, Z, Betke, KM, Yim, YY, Hyde, K, Rodriguez, S, Alford, S, Hamm, HE. Gbetagamma inhibits exocytosis via interaction with critical residues on soluble N-ethylmaleimide-sensitive factor attachment protein-25. Mol Pharmacol, 82(6), 1136-49 , 2012 PMCID: PMC3502621

Betke, KM, Wells, CA, Hamm, HE. GPCR mediated regulation of synaptic transmission. Prog Neurobiol, 96(3), 304-21, 2012 PMCID: PMC3319362

Preininger, AM, Kaya, AI, Gilbert, JA, Busenlehner, LS, Armstrong, RN, Hamm, HE. Myristoylation exerts direct and allosteric effects on Galpha conformation and dynamics in solution. Biochemistry, 51(9), 1911-24, 2012 PMCID: PMC3312377

Wells, CA, Betke, KM, Lindsley, CW, Hamm, HE. Label-free detection of G protein-SNARE interactions and screening for small molecule modulators. ACS Chem Neurosci, 3(1), 69-78, 2012 PMCID: PMC3285104

Ichikawa, J, Cole, HA, Magnussen, RA, Mignemi, NA, Butler, M, Holt, GE, O'Rear, L, Yuasa, M, Pabla, B, Haro, H, Cates, JM, Hamm, HE, Schwartz, HS, Schoenecker, JG. Thrombin induces osteosarcoma growth, a function inhibited by low molecular weight heparin in vitro and in vivo: Procoagulant nature of osteosarcoma. Cancer, 118(9), 2494-506 , 2011 PMID:21953059

Lenoci, L, Duvernay, M, Satchell, S, Dibenedetto, E, Hamm, HE. Mathematical model of PAR1-mediated activation of human platelets. Mol Biosyst, 7(4), 1129-37, 2011 PMID: 21229145

Kaya, AI, Thaker, TM, Preininger, AM, Iverson, TM, Hamm, HE. Coupling efficiency of rhodopsin and transducin in bicelles. Biochemistry, 50(15), 3193-203, 2011 PMCID: PMC3119548

Van Eps, N, AM Preininger, N Alexander, AI Kaya, S Meier, J Meiler, HE Hamm, WL Hubbell. Interaction of a G protein with an activated receptor opens the interdomain interface in the alpha subunit. . PNAS USA, 108(23), 9420-4, 2011 PMCID: PMC3111277

Caruso G, Bisegna P, Andreucci D, Lenoci L, Gurevich VV, Hamm HE, DiBenedetto E. Identification of key factors that reduce the variability of the single photon response. PNAS USA, 108(19), 7804-7, 2011 PMCID: PMC3093507

Holinstat M, Boutaud O, Apopa PL, Vesci J, Bala M, Oates JA, Hamm HE. Protease-activated receptor signaling in platelets activates cytosolic phospholipase A2I? differently for cyclooxygenase-1 and 12-lipoxygenase catalysis. Arterioscler Thromb Vasc Biol, 31(2), 435-42, 2011 PMCID: PMC3035574

Shen L, Caruso G, Bisegna P, Andreucci D, Gurevich VV, Hamm HE, Dibenedetto E. Dynamics of mouse rod phototransduction and its sensitivity to variation of key parameters. IET Syst Biol, 4(1), 12, 2010 PMID: 20001089

Jernigan, KK, Cselenyi, CS, Thorne, CA, Hanson, AJ, Tahinci, E, Hajicek, N, Oldham, WM, Lee, LA, Hamm, HE, Hepler, JR, Kozasa, T, Linder, ME, Lee, E. Gbetagamma activates GSK3 to promote LRP6-mediated beta-catenin transcriptional activity. Sci Signal, 3(121), ra37, 2010 PMCID: PMC3088111

Caruso G, Bisegna P, Lenoci L, Andreucci D, Gurevich VV, Hamm HE, DiBenedetto E. Kinetics of rhodopsin deactivation and its role in regulating recovery and reproducibility of rod photoresponse. PLoS Comput Biol, 6(12), e1001031, 2010 PMCID: PMC3002991

Mazzoni MR, Porchia F, Hamm HE. Proteolytic fragmentation for epitope mapping. Methods Mol Biol, 524, 77-86, 2009 PMID: 19377938

Preininger, AM, Funk, MA, Oldham, WM, Meier, SM, Johnston, CA, Adhikary, S, Kimple, AJ, Siderovski, DP, Hamm, HE, Iverson, TM. Helix Dipole Movement and Conformational Variability Contribute to Allosteric GDP Release in Galphai Subunits. Biochemistry, 48(12), 2630-42, 2009 PMID: 19222191

Hamm HE, Meier SM, Liao G, Preininger AM. Trp fluorescence reveals an activation-dependent cation-pi interaction in the Switch II region of Galphai proteins. Protein Sci, 18(11), 2326-35, 2009 PMCID: PMC2788287

Marjoram RJ, Voss B, Pan Y, Dickeson SK, Zutter MM, Hamm HE, and Santoro, SA. Suboptimal Activation of Protease-activated Receptors Enhances alpha2beta1 Integrin-mediated Platelet Adhesion to Collagen. J Biol Chem, 284(50), 34640-7, 2009 PMCID: PMC2787326

Preininger AM, Funk MA, Oldham WM, Meier SM, Johnston CA, Adhikary S, Kimple AJ, Siderovski DP, Hamm HE, Iverson TM. Helix dipole movement and conformational variability contribute to allosteric GDP release in Galphai subunits . Biochemistry, 48(12), 2630-42, 2009 PMCID: PMC2736342

Wen XH, Shen L, Brush RS, Michaud N, Al-Ubaidi MR, Gurevich VV, Hamm HE, Lem J, Dibenedetto E, Anderson RE, Makino CL. Overexpression of rhodopsin alters the structure and photoresponse of rod photoreceptors. Biophys J, 96(3), 939-50, 2009 PMCID: PMC2716671

Holinstat M, Preininger AM, Milne SB, Hudson WJ, Brown HA, Hamm HE. Irreversible platelet activation requires protease-activated receptor 1-mediated signaling to phosphatidylinositol phosphates. Mol Pharmacol, 76(2), 301-13, 2009 PMCID: PMC2713123

Lin F, Chen S, Sepich DS, Panizzi JR, Clendenon SG, Marrs JA, Hamm HE, Solnica-Krezel L. Galpha 12/13 regulate epiboly by inhibiting E-cadherin activity and modulating the actin cytoskeleton . J Cell Biol, 184(6), 909-21, 2009 PMCID: PMC2664974

Preininger, AM, Funk, MA, Oldham, WM, Meier, SM, Johnston, CA, Adhikary, S, Kimple, AJ, Siderovski, DP, Hamm, HE, Iverson, TM. Helix dipole movement and conformational variability contribute to allosteric GDP release in Galphai subunits. Biochemistry, 48(12), 2630-42, 2009

Lin, F, Chen, S, Sepich, DS, Panizzi, JR, Clendenon, SG, Marrs, JA, Hamm, HE, Solnica-Krezel, L. Galpha12/13 regulate epiboly by inhibiting E-cadherin activity and modulating the actin cytoskeleton. J Cell Biol, 184(6), 909-21, 2009

Marjoram, RJ, Voss, B, Pan, Y, Dickeson, SK, Zutter, MM, Hamm, HE, Santoro, SA. Suboptimal activation of protease-activated receptors enhances alpha2beta1 integrin-mediated platelet adhesion to collagen. J Biol Chem, 284(50), 34640-7, 2009

Hamm, HE, Meier, SM, Liao, G, Preininger, AM. Trp fluorescence reveals an activation-dependent cation-pi interaction in the Switch II region of Galphai proteins. Protein Sci, 18(11), 2326-35, 2009

Oldham WM, Hamm HE. Heterotrimeric G protein activation by G-protein-coupled receptors. Nat Rev Mol Cell Biol, 9(1), 60-71, 2008 PMID: 18043707

Yoon, EJ, Hamm, HE, Currie, KP. G protein betagamma Subunits Modulate the Number and Nature of Exocytotic Fusion Events in Adrenal Chromaffin Cells Independent of Calcium Entry. J Neurophysiol, 100(5), 2929-39, 2008 PMCID:2585407

Preininger AM, Parello J, Meier SM, Liao G, Hamm HE. Receptor-Mediated Changes at the Myristoylated Amino Terminus of Galpha(il) Proteins. Biochemistry, 47(39), 10281-93, 2008 PMCID: PMC2751642

Chen S, Lin F, Shin ME, Wang F, Shen L, Hamm HE. RACK1 Regulates Directional Cell Migration by Acting on Gbetagamma at the Interface with Its Effectors PLCbeta and P13Kgamma. Mol Biol Cell, 19(9), 3909-22, 2008 PMCID: PMC2526680

Bisegna P, Caruso G, Andreucci D, Shen L, Gurevich VV, Hamm HE, DiBenedetto E. Diffusion of the second messengers in the cytoplasm acts as a variability suppressor of the single photon response in vertebrate phototransduction. Biophys J, 94(9), 3363-83, 2008 PMCID: PMC2292384

Yoon, EJ, Hamm, HE, Currie, KP. G protein betagamma subunits modulate the number and nature of exocytotic fusion events in adrenal chromaffin cells independent of calcium entry. J Neurophysiol, 100(5), 2929-39, 2008

Preininger, AM, Parello, J, Meier, SM, Liao, G, Hamm, HE. Receptor-mediated changes at the myristoylated amino terminus of Galpha(il) proteins. Biochemistry, 47(39), 10281-93, 2008

Chen, S, Lin, F, Shin, ME, Wang, F, Shen, L, Hamm, HE. RACK1 regulates directional cell migration by acting on G betagamma at the interface with its effectors PLC beta and PI3K gamma. Mol Biol Cell, 19(9), 3909-22, 2008

Oldham WM, Hamm HE. How do receptors activate G proteins?. Adv Protein Chem, 74, 67-93, 2007 PMID: 17854655

Yoon EJ, Gerachshenko T, Spiegelberg BD, Alford S, Hamm HE. Gbetagamma Interferes with Ca2+-Dependent Binding of Synaptotagmin to the Soluble N-Ethylmaleimide-Sensitive Factor Attachment Protein Receptor (SNARE) Complex . Mol Pharmacol, 72(5), 1210-9, 2007 PMID: 17715396

Bilodeau, ML, Hamm, HE. Regulation of protease-activated receptor (PAR) 1 and PAR4 signaling in human platelets by compartmentalized cyclic nucleotide actions. J Pharmacol Exp Ther, 322(2), 778-88, 2007 PMID: 17525299

Voss, B, McLaughlin, JN, Holinstat, M, Zent, R, Hamm, HE. PAR1, but not PAR4, activates human platelets through a Gi/o/phosphoinositide-3 kinase signaling axis. Mol Pharmacol, 71(5), 1399-406, 2007 PMID: 17303701

Huang, K, Voss, B, Kumar, D, Hamm, HE, Harth, E. Dendritic Molecular Transporters Provide Control of Delivery to Intracellular Compartments. Bioconjug Chem, 18(2), 403-9, 2007 PMID: 17284011

Spiegelberg BD, Hamm HE. Roles of G-protein-coupled receptor signaling in cancer biology and gene transcription. Curr Opin Genet Dev, 17(1), 40-4, 2007 PMID: 17188489

Holinstat, M, Voss, B, Bilodeau, ML, Hamm, HE. Protease-Activated Receptors Differentially Regulate Human Platelet Activation through a Phosphatidic Acid-Dependent Pathway. Mol Pharmacol, 71(3), 686-94, 2007 PMID: 17151288

Oldham WM, Van Eps N, Preininger AM, Hubbell WL, Hamm HE. Mapping allosteric connections from the receptor to the nucleotide-binding pocket of heterotrimeric G proteins. Proc Natl Acad Sci USA, 104(19), 7927-32, 2007 PMCID: PMC1876549

Yoon, EJ, Gerachshenko, T, Spiegelberg, BD, Alford, S, Hamm, HE. Gbetagamma interferes with Ca2+-dependent binding of synaptotagmin to the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. Mol Pharmacol, 72(5), 1210-9, 2007

Oldham, WM, Van Eps, N, Preininger, AM, Hubbell, WL, Hamm, HE. Mapping allosteric connections from the receptor to the nucleotide-binding pocket of heterotrimeric G proteins. Proc Natl Acad Sci U S A, 104(19), 7927-32, 2007

Chen S, Hamm HE. DEP domains: More than just membrane anchors. Dev Cell, 11(4), 436-8, 2006 PMID: 17011483

Oldham WM, Hamm HE. Structural basis of function in heterotrimeric G proteins. Q Rev Biophys, 39(2), 117-66, 2006 PMID: 16923326

Oldham WM, Van Eps N, Preininger AM, Hubbell WL, Hamm HE. Mechanism of the receptor-catalyzed activation of heterotrimeric G proteins. Nat Struct Mol Biol, 13(9), 772-7, 2006 PMID: 16892066

Holinstat M, Voss B, Bilodeau ML, McLaughlin JN, Cleator J, Hamm HE. PAR4, but not PAR1, signals human platelet aggregation via Ca2+ mobilization and synergistic P2Y12 receptor activation. J Biol Chem, 281(36), 26665-74, 2006 PMID: 16837456

Ding J, Guzman JN, Tkatch T, Chen S, Goldberg JA, Ebert PJ, Levitt P, Wilson CJ, Hamm HE, Surmeier DJ. RGS4-dependent attenuation of M4 autoreceptor function in striatal cholinergic interneurons following dopamine depletion. Nat Neurosci, 9(6), 832-42, 2006 PMID: 16699510

Preininger AM, Henage LG, Oldham WM, Yoon EJ, Hamm HE, Brown HA. Direct Modulation of Phospholipase D Activity by Gbetagamma. Mol Pharmacol, 70(1), 311-8, 2006 PMID: 16638972

Bilodeau ML, Hamm HE. Endothelial nitric-oxide synthase reveals a new face in G protein signaling. Mol Pharmacol, 69(3), 677-9, 2006 PMID: 16377762

Georgoussi Z, Leontiadis L, Mazarakou G, Merkouris M, Hyde K, Hamm H. Selective interactions between G protein subunits and RGS4 with the C-terminal domains of the mu- and delta-opiod receptors regulate opioid receptor signaling. Cell Signal, 18(6), 771-82, 2006 PMID: 16120478

Cleator JH, Zhu WQ, Vaughan DE, Hamm HE. Differential regulation of endothelial exocytosis of P-selectin and von Willebrand factor by protease-activated receptors and cAMP. Blood, 107(7), 2736-44, 2006 PMCID: PMC1895372

Murphy SC, Harrison T, Hamm HE, Lomasney JW, Mohandas N, Haldar K. Erythrocyte G protein as a novel target for malarial chemotherapy. PLoS Med, 3(12), e528, 2006 PMCID: PMC1716186

Van Eps N, Oldham WM, Hamm HE, Hubbell WL. Structural and dynamical changes in an alpha-subunit of a heterotrimeric G protein along the activation pathway. Proc Natl Acad Sci USA, 103(44), 16194-9, 2006 PMCID: PMC1637559

Holinstat M, Oldham WM, Hamm HE. G-protein-coupled receptors: evolving views on physiological signalling: symposium on G-protein-coupled receptors: evolving concepts and new techniques. EMBO Rep, 7(9), 866-9, 2006 PMCID: PMC1559677

Caruso G, Bisegna P, Shen L, Andreucci D, Hamm HE, DiBenedetto E. Modeling the role of incisures in vertebrate phototransduction. Biophys J, 91(4), 1192-212, 2006 PMCID: PMC1518654

Photowala H, Blackmer T, Schwartz E, Hamm HE, Alford S. G protein betagamma-subunits activated by serotonin mediate presynaptic inhibition by regulating vesicle fusion properties. Proc Natl Acad Sci USA, 103(11), 4281-6, 2006 PMCID: PMC1449684

Caruso G, Khanal H, Alexiades V, Rieke F, Hamm HE, DiBenedetto E. Mathematical and computational modelling of spatio-temporal signalling in rod phototransduction. Syst Biol (Stevenage), 152(3), 119-37, 2005 PMID: 16986276

Spiegelberg BD, Hamm HE. Gbetagamma Binds Histone Deacetylase 5 (HDAC5) and Inhibits Its Transcriptional Co-repression Activity. J Biol Chem, 280(50), 41769-76, 2005 PMID: 16221676

Chen S, Lin F, Hamm HE. RACK1 Binds to a Signal Transfer Region of Gbetagamma and Inhibits Phospholipase C beta2 activation. J Biol Chem, 280(39), 33445-52, 2005 PMID: 16051595

McLaughlin JN, Shen L, Holinstat M, Brooks JD, Dibenedetto E, Hamm HE. Functional selectivity of G protein signaling by agonist peptides and thrombin for the protease-activated receptor-1. J Biol Chem, 280(26), 25048-59, 2005 PMID: 15878870

Gerachshenko T, Blackmer T, Yoon EJ, Bartleson C, Hamm HE, Alford S. Gbetagamma acts at the C terminus of SNAP-25 to mediate presynaptic inhibition. Nat Neurosci, 8(5), 597-605, 2005 PMID: 15834421

McLaughlin JN, Mazzoni MR, Cleator JH, Earls L, Perdigoto AL, Brooks JD, Muldowney JA, Vaughan DE, Hamm HE. Thrombin modulates the expression of a set of genes including thrombospondin-1 in human microvascular endothelial cells. J Biol Chem, 280(23), 22172-80, 2005 PMID: 15817447

Blackmer T, Larsen EC, Bartleson C, Kowalchyk JA, Yoon EJ, Preininger AM, Alford S, Hamm HE, Martin TF. G protein betagamma directly regulates SNARE protein fusion machinery for secretory granule exocytosis. Nat Neurosci, 8(4), 421-5, 2005 PMID: 15778713

Lin F, Sepich DS, Chen S, Topczewski J, Yin C, Solnica-Krezel L, Hamm H. Essential roles of Galpha 12/13 signaling in distinct cell behaviors driving zebrafish convergence and extension gastrulation movements . J Cell Biol, 169(5), 777-87, 2005 PMCID: PMC2171618

Lukov GL, Hu T, McLaughlin JN, Hamm HE, Willardson BM. Phosducin-like protein acts as a molecular chaperone for G protein betagamma dimer assembly. EMBO J, 24(11), 1965-75, 2005 PMCID: PMC1142607

Chen S, Spiegelberg BD, Lin F, Dell EJ, Hamm HE. Interaction of Gbetagamma with RACK1 and other WD40 repeat proteins. J Mol Cell Cardiol, 37(2), 399-406, 2004 PMID: 15276010

Srinivasan C, Toon J, Amari L, Abukhdeir AM, Hamm HE, Geraldes CF, Ho YK, Mota de Freitas D. Competition between lithium and magnesium ions for the G-protein transducin in the guanosine 5'-diphosphate bound conformation. J Inorg Biochem, 98(5), 691-701, 2004 PMID: 15134914

Chen S, Dell EJ, Lin F, Sai J, Hamm HE. RACK1 Regulates Specific Functions of Gbetagamma. J Bio Chem, 279(17), 17861-8, 2004 PMID: 14963031

Preininger AM, Hamm HE. G protein signaling: insights from new structures. Sci STKE, 2004(218), re3, 2004 PMID: 14762218

Cabrera-Vera TM, Hernandez S, Earls LR, Medkova M, Sundgren-Andersson AK, Surmeier DJ, Hamm HE. RGS9-2 modulates D2 dopamine receptor-mediated Ca2+ channel inhibition in rat striatal cholinergic interneurons . Proc Natl Acad Sci USA, 16(46), 16339-44, 2004 PMCID: PMC528982

Cabrera-Vera TM, Vanhauwe J, Thomas TO, Medkova M, Preininger A, Mazzoni MR, Hamm HE. Insights into G protein structure, function, and regulation. Endocr Rev, 24(6), 765-81, 2003 PMID: 14671004

Slessareva JE, Ma H, Depree KM, Flood LA, Bae H, Cabrera-Vera TM, Hamm HE, Graber SG. Closely related G protein coupled receptors use multiple and distinct domains on G protein alpha-subunits for selective coupling. J Biol Chem, 278(50), 50530-6, 2003 PMID: 14525988

Harrison T, Samuel BU, Akompong T, Hamm H, Mohandas N, Lomasney JW, Haldar K. Erythrocyte G protein-coupled receptor signaling in malarial infection. Science, 301(5640), 1734-6, 2003 PMID: 14500986

Preininger AM, Van Eps N, Yu N-J, Medkova M, Hubbell WL, Hamm HE. The myristoylated amino terminus of Galpha(i)(1) plays a critical role in the structure and function of Galpha(i)(1) subunits in solution. Biochemistry, 42(26), 7931-41, 2003 PMID: 12834345

Chen NF, Yu JZ, Skiba NP, Hamm HE, Rasenick MM. A Specific Domain of Gialpha Required for the Transactivation of Gialpha by Tubulin Is Implicated in the Organization of Cellular Microtubules. J Biol Chem, 278(17), 15285-90, 2003 PMID: 12582171

Andreucci D, Bisegna P, Caruso G, Hamm HE, DiBenedetto E. Mathematical model of the spatio-temporal dynamics of second messengers in visual transduction. Biophys J, 85(3), 1358-76, 2003 PMCID: PMC1303314

Dell EJ, Connor J, Chen S, Stebbins EG, Skiba NP, Mochly-Rosen D, Hamm HE. The betagamma subunit of heterotrimeric G proteins interacts with RACK1 and two other WD repeat proteins. J Biol Chem, 277(51), 49888-95, 2002 PMID: 12359736

Medkova M, Preininger AM, Yu N-J, Hubbell WL, Hamm HE. Conformational Changes in the Amino-Terminal Helix of the G Protein alpha(i)(1) Following Dissociation From Gbetagamma Subunit and Activation. Biochemistry, 41(31), 9962-72, 2002 PMID: 12146960

Vanhauwe JF, Thomas TO, Minshall RD, Tiruppathi C, Li A, Gilchrist A, Yoon EJ, Malik AB, Hamm HE. Thrombin Receptors Activate Go Proteins in Endothelial Cells to Regulate Intracellular Calcium and Cell Shape Changes. J Biol Chem, 277(37), 34143-9, 2002 PMID: 12039967

Mukherjee S, Gurevich VV, Preninger A, Hamm HE, Bader M-F, Fazleabas AT, Birnbaumer L, Hunzicker-Dunn M. Aspartic acid 564 in the third cytoplasmic loop of the luteinizing hormone/ choriogonadotropin receptor is crucial for phosphorylation-independent interaction with arrestin2. J Biol Chem, 277(20), 17916-27, 2002 PMID: 11867621

Gilchrist A, Li A, Hamm HE. G(alpha) COOH-terminal minigene vectors dissect heterotrimeric G protein signaling. Sci STKE, 2002(118), PL1, 2002 PMID: 11836477

Cabrera-Vera TM, Thomas TO, Vanhauwe J, Depree KM, Graber SG, Hamm HE. Dissecting receptor-G protein specificity using G alpha chimeras. Methods Enzymol, 344, 69-81, 2002 PMID: 11771421

Schey KL, Busman M, Cook LA, Hamm HE, Hildebrandt JD. Structural characterization of intact G protein gamma subunits by mass spectrometry. Methods Enzymol, 344, 586-97, 2002 PMID: 11771413

Gilchrist A, Li Anli, Hamm HE. Design and use of C-terminal minigene vectors for studying role of heterotrimeric G proteins. Methods Enzymol, 344, 58-69, 2002 PMID: 11771412

Dell EJ, Blackmer T, Skiba NP, Daaka Y, Shekter LR, Rosal R, Reuveny E, Hamm HE. Defining G protein betagamma specificity for effector recognition. Methods Enzymol, 344, 421-34, 2002 PMID: 11771401

Thomas TO, Hamm HE. An Intramolecular Contact in Galpha Transducin That Participates in Maintaining Its Intrinsic GDP Release Rate. Mol Cell Biol Res Commun, 4(5), 282-91, 2001 PMID: 11529678

Minadeo N, Layden B, Amari LV, Thomas V, Radloff K, Srinivasan C, Hamm HE, de Freitas DM. Effect of Li+ upon the Mg2+-Dependent Activation of Recombinant G(i)alpha(1) . Arch Biochem Biophys, 388(1), 7-12, 2001 PMID: 11361143

Thulin CD, Savage JR, McLaughlin JN, Truscott SM, Old WM, Ahn NG, Resing KA, Hamm HE, Bitensky MW, nd Willardson BM. Modulation of the G Protein Regulator Phosducin by Ca 2+ /Calmodulin-dependent Protein Kinase II Phosphorylation and 14-3-3 Protein Binding. J Biol Chem, 276(26), 23805-23815, 2001 PMID: 11331285

Blackmer T, Larsen EC, Takahashi M, Martin TF, Alford S, Hamm HE. G protein betagamma Subunit-Mediated Presynaptic Inhibition: Regulation of Exocytotic Fusion Downstream of Ca2+ Entry. Science, 292(5515), 293-7, 2001 PMID: 11303105

Gilchrist A, Vanhauwe JF, Li A, Thomas TO, Voyno-Yasenetskaya T, Hamm HE. Galpha Minigenes Expressing C-terminal Peptides Serve as Specific Inhibitors of Thrombin-mediated Endothelial Activation. J Biol Chem, 276(28), 25672-9, 2001 PMID: 11274183

Lopez I, Mak EC, Ding J, Hamm HE, Lomasney JW. A novel bifunctional phospholipase c that is regulated by Galpha12 and Stimulates the Ras/Mitogen-activated Protein Kinase Pathway. J Biol Chem, 276(4), 2758-65, 2001 PMID: 11022047

Aris L, Gilchrist A, Rens-Domiano S, Meyer C, Schatz PJ, Dratz EA, Hamm HE. Structural Requirements for the Stabilization of Metarhodopsin II by the C Terminus of the alpha subunit of Transducin. J Biol Chem, 276(4), 2333-9, 2001 PMID: 11018024

Hamm HE. How activated receptors couple to G proteins. Proc Natl Acad Sci USA, 98(9), 4819-21, 2001 PMCID: PMC33117

Savage JR, McLaughlin JN, Skiba NP, Hamm HE, Willardson BM. Functional roles of the two domains of phosducin and phosducin-like protein. J Biol Chem, 275(39), 30399-407, 2000 PMID: 10896945

Mazzoni MR, Taddei S, Giusti L, Rovero P, Galoppini C, DUrsi A, Albrizio S, Triolo A, Novellino E, Greco G, Lucacchini A, Hamm HE. A Galpha(8) carboxyl-terminal peptide prevents G(8) activation by the A(2)(A) adenosine receptor. Mol Pharmacol, 58(1), 226-36, 2000 PMID: 10860945

Skiba NP, Thomas TO, Hamm HE. Galpha t/G alpha(i)(1) chimeras used to define structural basis of specific functions of Galpha t. Methods Enzymol, 315, 502-24, 2000 PMID: 10736723

Yang CS, Skiba NP, Mazzoni MR, Thomas TO, Hamm HE. Fluorescent probes as indicators of conformation changes in transducin on activation. Methods Enzymol, 315, 490-502, 2000 PMID: 10736722

Gilchrist A, Li A, Hamm HE. Use of peptides-on-plasmids combinatorial library to identify high-affinity peptides that bind rhodopsin. Methods Enzymol, 315, 388-404, 2000 PMID: 10736715

Minshall RD, Tiruppathi C, Vogel SM, Niles WD, Gilchrist A, Hamm HE, Malik AB. Endothelial Cell-surface gp60 Activates Vesicle Formation and Trafficking via Gi-coupled Src Kinase Signaling Pathway. J Cell Biol, 150(5), 1057-70, 2000 PMCID: PMC2175246

Yang CS, Skiba NP, Mazzoni MR, Hamm HE. Conformational Changes at The Carboxyl Terminus of Galpha Occur during G Protein Activation. J Biol Chem, 274(4), 2379-85, 1999 PMID: 9891006

Bae H, Cabrera-Vera TM, Depree KM, Graber SG, Hamm HE. Two Amino Acids within the alpha4 Helix of Galpha(i)(1) mediate Coupling with 5-Hydroxytryptamine 1B Receptors. J Biol Chem, 274(21), 14963-71, 1999 PMID: 10329698

Ellis CA, Malik AB, Gilchrist A, Hamm HE, Sandoval R, Voyno-Yasenetskaya T, Tiruppathi c. Thrombin Induces Proteinase-activated Receptor-1 Gene Expression in Endothelial Cells via Activation of Gi-linked Ras/ Mitogen-activated Protein Kinase Pathway*. J Biol Chem, 274(19), 13718-27, 1999 PMID: 10224146

Skiba NP, Yang CS, Huang T, Bae H, Hamm HE. The alpha-Helical Domain of Galpha(t) Determines Specific Interaction with Regulator of G Protein Signaling 9. J Biol Chem, 274(13), 8770-8, 1999 PMID: 10085118

Gilchrist A, Bunemann M, Li A, Hosey MM, Hamm HE. A dominant-negative strategy for studying roles of G proteins in vivo. J Biol Chem, 274(10), 6610-6, 1999 PMID: 10037756

Gilchrist A, Mazzoni MR, Dineen B, Dice A, Linden J, Proctor WR, Lupica CR, Dunwiddie TV, Hamm HE. Antagonists of the Receptor-G Protein Interface Block Gi-coupled Signal Transduction. J Biol Chem, 273(24), 14912-9, 1998 PMID: 9614095

Ford CE, Skiba NP, Bae H, Daaka Y, Reuveny E, Shekter LR, Rosal R, Weng G, Yang CS, Iyengar R, Miller RJ, Jan LY, Lefkowitz RJ, Hamm HE. Molecular basis for interactions of G protein betagamma subunits with effectors. Science, 280(5367), 1271-4, 1998 PMID: 9596582

Skiba NP, Hamm HE. How Gsalpha activates adenylyl cyclase. Nat Struct Biol, 5(2), 88-92, 1998 PMID: 9461067

Hamm HE. The many faces of G protein signaling. J Biol Chem, 273(2), 669-72, 1998 PMID: 9422713

Bae H, Anderson K, Flood LA, Skiba NP, Hamm HE, Graber SG. Molecular determinants of selectivity in 5-hydroxytryptamine1B receptor-G protein interactions. J Biol Chem, 272(51), 32071-7, 1997 PMID: 9405403

Nekrasova ER, Berman DM, Rustandi RR, Hamm HE, Gilman AG, Arshavsky VY. Activation of transducin guanosine triphosphatase by two proteins of the RGS family. Biochemistry, 36(25), 7638-43, 1997 PMID: 9201904

Mazzoni MR, Artemyev NO, Hamm HE. Proteolytic fragmentation for epitope mapping. Methods Mol Biol, 66, 109-20, 1996 PMID: 8959709

Mazzoni MR, Hamm HE. Interaction of transducin with light-activated rhodopsin protects It from proteolytic digestion by trypsin. J Biol Chem, 271(47), 30034-40, 1996 PMID: 8939950

Artemyev NO, Surendran R, Lee JC, Hamm HE. Subunit structure of rod cGMP-phosphodiesterase. J Biol Chem, 271(41), 25382-8, 1996 PMID: 8810304

Hamm HE, Gilchrist A. Heterotrimeric G proteins. Curr Opin Cell Biol, 8(2), 189-96, 1996 PMID: 8791425

Suh KH, Hamm HE. Cyclic AMP-Dependent Phosphoprotein Components I and II Interact with betagamma Subunits of Transducin in Frog Rod Outer Segments. Biochemistry, 35(1), 290-8, 1996 PMID: 8555187

Sondek J, Bohm A, Lambright DG, Hamm HE, Sigler PB. Crystal structure of a G-protein betagamma dimer at 2.1A resolution. Nature, 379(6568), 369-74, 1996 PMID: 8552196

Lambright DG, Sondek J, Bohm A, Skiba NP, Hamm HE, Sigler PB. The 2.0 A crystal structure of a heterotrimeric G protein. Nature, 379(6563), 311-9, 1996 PMID: 8552184

Skiba NP, Bae H, Hamm HE. Mapping of effector binding sites of transducin alpha-subunit using Galpha(t)/Galpha(i)(1) chimeras. J Biol Chem, 271(1), 413-24, 1996 PMID: 8550597

Martin EL, Rens-Domiano S, Schatz PJ, Hamm HE. Potent peptide analogues of a G protein receptor-binding region obtained with a combinatorial library. J Biol Chem, 271(1), 361-6, 1996 PMID: 8550587

Artemyev NO, Natochin M, Busman M,Schey KL, Hamm HE. Mechanism of photoreceptor cGMP phosphodiesterase inhibition by its gamma subunits. Biochemistry, 93(11), 5407-12, 1996 PMCID: PMC39259

Slepak, V Z, Artemyev, N O, Zhu, Y, Dumke, C L, Sabacan, L, Sondek, J, Hamm, H E, Bownds, M D, and Arshavsky, V Y. An Effector Site That Stimulates G-protein GTPase in Photoreceptors. J Biol Chem, 270(24), 14319-14324, 1995 PMID: 7782290

Skiba NP, Artemyev NO, Hamm HE. The carboxyl terminus of the gamma-subunit of rod cGMP phosphodiesterase contains distinct sites of interaction with the enzyme catalytic subunits and the alpha-subunit of transducin. J Biol Chem, 270(22), 13210-5, 1995 PMID: 7768919

Rens-Domiano S, Hamm HE. Structural and functional relationships of heterotrimeric G-proteins. FASEB J, 9(11), 1059-66, 1995 PMID: 7649405

Lambright, D G, Noel, J P, Hamm, H E, Sigler, P B. Structural determinants for activation of the alpha-subunit of a heterotrimeric G protein. Nature, 369(6482), 621-8, 1994 PMID: 8208289

Sondek, J, Lambright, D G, Noel, J P, Hamm, H E, Sigler, P B. GTPase mechanism of Gproteins from the 1.7-A crystal structure of transducin alpha-GDP-AIF-4. Nature, 372(6503), 276-9, 1994 PMID: 7969474

Hamm, H E, Rarick, H M. Specific peptide probes for G-protein interactions with receptors. Methods Enzymol, 237, 423-36, 1994 PMID: 7935015

Rarick, H M, Artemyev, N O, Mills, J S, Skiba, N P, Hamm, H E. Specific peptide probes for G-protein interaction with effectors. Methods Enzymol, 238, 13-28, 1994 PMID: 7799779

Artemyev, N O, Hamm, H E. Probing G-protein function. Nat Struct Biol, 1(11), 752-4, 1994 PMID: 7634081

Arshavsky, V Y, Dumke, C L, Zhu, Y, Artemyev, N O, Skiba, N P, Hamm, H E, Bownds, M D. Regulation of transducin GTPase activity in bovine rod outer segments. J Biol Chem, 269(31), 19882-87, 1994

Rasenick, M M, Watanabe, M, Lazarevic, M B, Hatta, S, Hamm, H E. Synthetic peptides as probes for G protein function. Carboxyl-terminal G alpha s peptides mimic Gs and evoke high affinity agonist binding to beta-adrenergic receptors. J Biol Chem, 269(34), 21519-25, 1994

Krupnick, J G, Gurevich, V V, Schepers, T, Hamm, H E, Benovic, J L. Arrestin-rhodopsin interaction. Multi-site binding delineated by peptide inhibition. J Biol Chem, 269(5), 3226-32, 1994

Mazzoni, M R, Hamm, H E. Tryptophan207 is involved in the GTP-dependent conformational switch in the alpha subunit of the G protein transducin: chymotryptic digestion patterns of the GTP gamma S and GDP-bound forms. J Protein Chem, 12(2), 215-21, 1993 PMID: 8489707

Dratz, EA, Furstenau, JE, Lambert, CG, Thireault, DL, Rarick, HR, Schepers, T, Pakhlevaniants, S., and H.E. Hamm. NMR structure of a receptor bound G protein peptide. Nature, 363(6426), 276-281, 1993 PMID: 8487866

Hargrave, P A, Hamm, H E, Hofmann, K P. Interaction of rhodopsin with the G-protein, transducin. Bioessays, 15(1), 43-50, 1993 PMID: 8466475

Noel JP, Hamm HE, Sigler PB. The 2.2 A crystal structure of transducin-alpha complexed with GTPgammaS. Nature, 366(6456), 654-63, 1993 PMID: 8259210

Artemyev, N O, Mills, J S, Thornburg, K R, Knapp, D R, Schey, K L, Hamm, H E. A site on transducin alpha-subunit of interaction with the polycationic region of cGMP phosphodiesterase inhibitory subunit. J Biol Chem, 268(31), 23611-15, 1993

Rarick HM, Artemyev NO, Hamm HE. A site on rod G protein alpha subunit that mediates effector activation. Science, 256(5059), 1031-3, 1992 PMID: 1317058

Stieve, H, Niemeyer, B, Aktories, K, Hamm, H E. Disturbing GTP-binding protein function through microinjection into the visual cell of Limulus. Z Naturforsch C, 47(11-12), 915-21, 1992 PMID: 1285831

Artemyev, N O, Hamm, H E. Two-site high-affinity interaction between inhibitory and catalytic subunits of rod cyclic GMP phosphodiesterase. Biochem J, 283(Pt 1), 273-9, 1992 PMCID: PMC1131025

Mangels, L A, Neubig, R R, Hamm, H E, Gnegy, M E. Calmodulin binding distinguishes between betagamma subunits of activated G proteins and transducin. Biochem J, 283(Pt 3), 683-90, 1992 PMCID: PMC1130940

Artemyev, N O, Rarick, H M, Mills, J S, Skiba, N P, Hamm, H E. Sites of interaction between rod G-protein alpha-subunit and cGMP-phosphodiesterase gamma-subunit. Implications for the phosphodiesterase activation mechanism. J Biol Chem, 267(35), 25067-72, 1992

Hamm, H E. Molecular interactions between the photoreceptor G protein and rhodopsin. Cell Mol Neurobiol, 11(6), 563-78, 1991 PMID: 1782650

Warpeha, K M, Hamm, H E, Rasenick, M M, Kaufman, L S. A blue-light-activated GTP-binding protein in the plasma membranes of etiolated peas. Proc Natl Acad Sci USA, 88, 8925-8929, 1991 PMCID: PMC52623

Mazzoni, M R, Malinski, J A, Hamm, H E. Structural analysis of rod GTP-binding protein, Gt. Limited proteolytic digestion pattern of Gt with four proteases defines monoclonal antibody epitope. J Biol Chem, 266(21), 14072-81, 1991

Hamm, H E, Rarick, H, Mazzoni, M, Malinski, J, Suh, K H. The molecular basis of GTP-binding protein interaction with receptors. Biochem Soc Symp, 56, 35-44, 1990 PMID: 2256961

Hamm, H E. Surfaces of interaction between Gt and rhodopsin in the GDP-bound and empty-pocket configurations. Adv Second Messenger Phosphoprotein Res, 24, 76-82, 1990 PMID: 2119661

Robinson, P R, Wood, S F, Szuts, E Z, Fein, A, Hamm, H E, Lisman, J E. Light-dependent GTP-binding proteins in squid photoreceptors. Biochem j, 272(1), 79-85, 1990 PMCID: PMC1149659

Mazzoni, M R, Hamm, H E. Effect of monoclonal antibody binding on alpha-beta gamma subunit interactions in the rod outer segment G protein, Gt. Biochemistry, 28(25), 9873-80, 1989 PMID: 2482080

Pepe, I M, Panfoli, I, Hamm, H E. Visual transduction in vertebrate photoreceptors. Light activation of guanylate cyclase. Cell Biophys, 14(2), 129-37, 1989 PMID: 2472205

Hamm, H E, Deretic, D, Mazzoni, M R, Moore, C A, Takahashi, J S, Rasenick, M M. A monoclonal antibody against the rod outer segment guanyl nucleotide-binding protein, transducin, blocks the stimulatory and inhibitory G proteins of adenylate cyclase. J Biol Chem, 264(19), 11475-82, 1989

Hamm HE, Deretic D, Arendt A, Hargrave PA, Koenig B, Hofmann KP. Site of G protein binding to rhodopsin mapped with synthetic peptides from the alpha subunit. Science, 241(4867), 832-5, 1988 PMID: 3136547

Yatani, A, Hamm, H, Codina, J, Mazzoni, M R, Birnbaumer, L, Brown, A M. A monoclonal antibody to the alpha subunit of Gk blocks muscarinic activation of atrial K+ channels. Science, 241(4867), 828-31, 1988 PMID: 2457252

Deretic, D, Hamm, H E. Topographic analysis of antigenic determinants recognized by monoclonal antibodies to the photoreceptor guanyl nucleotide-binding protein, transducin. J Biol Chem, 262(22), 10839-47, 1987 PMID: 2440876

Hamm, H E, Deretic, D, Hofmann, K P, Schleicher, A, Kohl, B. Mechanism of action of monoclonal antibodies that block the light activation of the guanyl nucleotide-binding protein, transducin. J Biol Chem, 262(22), 10831-8, 1987 PMID: 2440875

Hamm, H E, Bownds, M D. Protein complement of rod outer segments of frog retina. Biochemistry, 25(16), 4512-23, 1986 PMID: 3021191

Witt, P L, Hamm, H E, Bownds, M D. Preparation and characterization of monoclonal antibodies to several frog rod outer segment proteins. J Gen Physiol, 84(2), 251-63, 1984 PMCID: PMC2228734

Hamm, H E, Bownds, M D. A monoclonal antibody to guanine nucleotide binding protein inhibits the light-activated cyclic GMP pathway in frog rod outer segments. J Gen Physiol, 84(2), 265-280, 1984 PMCID: PMC2228732

Hamm, H E, Takahashi, J S, Menaker, M. Light-induced decrease of serotonin N-acetyltransferase activity and melatonin in the chicken pineal gland and retina. Brain Res, 266(2), 287-93, 1983 PMID: 6871664

Hermolin, J, Karell, M A, Hamm, H E, Bownds, M D. Calcium and cyclic GMP regulation of light-sensitive protein phosphorylation in frog photoreceptor membranes. J Gen Physiol, 79(4), 633-55, 1982 PMCID: PMC2215482

Hamm, H E, Menaker, M. Pineal and retinal serotonin N-acetyltransferase activity: modulation by phosphate. J Neurochem, 37, 1567-72, 1981 PMID: 7334376

Hamm, H E, Menaker, M. Retinal rhythms in chicks: circadian variation in melantonin and serotonin N-acetyltransferase activity. Proc Natl Acad Sci USA, 77(8), 4998-5002, 1980 PMCID: PMC349977