Melvin I. Simon

TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanisms (2009)

Imamachi, Noritaka, Park, Goon Ho, Lee, Hyosang, Anderson, David J., Simon, Melvin I., Basbaum, Allan I., ...

The mechanisms that generate itch are poorly understood at both the molecular and cellular levels despite its clinical importance. To explore the peripheral neuronal mechanisms underlying itch, we...

Markus Beu (13), Clinic of Nuclear Medicine, (2009)

John N. Abelson, Melvin I. Simon, Sidney P. Colowick, Nathan O. Kaplan, David L. Alexoff, ...

Contributors to Volume 385 Article numbers are in parentheses and following the names of contributors. Affiliations listed are current.

Molecular architecture of Gαo and the structural basis for RGS16-mediated deactivation (2008)

Slep, Kevin C., Kercher, Michele A., Wieland, Thomas, Chen, Ching-Kang, Simon, Melvin I., Sigler, Paul B.

Heterotrimeric G proteins relay extracellular cues from heptahelical transmembrane receptors to downstream effector molecules. Composed of an α subunit with intrinsic GTPase activity and a βγ...

The Alliance for Cellular Signaling Plasmid Collection A FLEXIBLE RESOURCE FOR PROTEIN LOCALIZATION STUDIES AND SIGNALING PATHWAY ANALYSIS * □S (2008)

Joelle R. Zavzavadjian, Sam Couture, Wei Sun Park, James Whalen, Shankar Subramaniam, Tobias Meyer, ...

Cellular responses to inputs that vary both temporally and spatially are determined by complex relationships between the components of cell signaling networks. Analysis of these relationships...

A versatile approach to multiple gene RNA interference using microRNA-based short hairpin RNAs (2007)

Zhu, Xiaocui, Santat, Leah A., Chang, Mi Sook, Liu, Jamie, Zavzavadjian, Joelle R., Wall, Estelle A., ...

Background: Effective and stable knockdown of multiple gene targets by RNA interference is often necessary to overcome isoform redundancy, but it remains a technical challenge when working with...

A versatile approach to multiple gene RNA interference using microRNA-based short hairpin RNAs (2007)

Zhu, Xiaocui, Santat, Leah A, Chang, Mi, Liu, Jamie, Zavzavadjian, Joelle R, Wall, Estelle A, ...

Abstract Background Effective and stable knockdown of multiple gene targets by RNA interference is often necessary to overcome isoform redundancy, but it remains a technical challenge when working...

Identification of an alternative G{alpha}q-dependent chemokine receptor signal transduction pathway in dendritic cells and granulocytes (2007)

Shi, Guixiu, Partida-Sánchz, Santiago, Misra, Ravi S., Tighe, Michael, Borchers, Michael T., Lee, James J., ...

CD38 controls the chemotaxis of leukocytes to some, but not all, chemokines, suggesting that chemokine receptor signaling in leukocytes is more diverse than previously appreciated. To determine the...

G{alpha}i2-mediated signaling events in the endothelium are involved in controlling leukocyte extravasation (2007)

Pero, Ralph S., Borchers, Michael T., Spicher, Karsten, Ochkur, Sergei I., Sikora, Ludmila, Rao, Savita P., ...

The trafficking of leukocytes from the blood to sites of inflammation is the cumulative result of receptor-ligand-mediated signaling events associated with the leukocytes themselves as well as with...

The Alliance for Cellular Signaling Plasmid Collection: A Flexible Resource for Protein Localization Studies and Signaling Pathway Analysis (2007)

Zavzavadjian, Joelle R., Coutre, Sam, Park, Wei Sun, Whalen, James, Lyon, Stephen, Lee, Genie, ...

Cellular responses to inputs that vary both temporally and spatially are determined by complex relationships between the components of cell signaling networks. Analysis of these relationships...

A single lentiviral vector platform for microRNA-based conditional RNA interference and coordinated transgene expression (2006)

Shin, Kum-Joo, Wall, Estelle A., Zavzavadjian, Joelle R., Santat, Leah A., Liu, Jamie, Hwang, Jong-Ik, ...

RNAi is proving to be a powerful experimental tool for the functional annotation of mammalian genomes. The full potential of this technology will be realized through development of approaches...

Structural and chemical requirements for histidine phosphorylation by the chemotaxis kinase CheA (2005)

Quezada, Cindy M., Hamel, Damon J., Gradinaru, Cristian, Bilwes, Alexandrine M., Dahlquist, Frederick W., Crane, Brian R., ...

The CheA histidine kinase initiates the signal transduction pathway of bacterial chemotaxis by autophosphorylating a conserved histidine on its phosphotransferase domain (P1). Site-directed mutations...

In different organisms, the mode of interaction between two signaling proteins is not necessarily conserved (2004)

Park, Sang-Youn, Beel, Bryan D., Simon, Melvin I., Bilwes, Alexandrine M., Crane, Brian R.

Although interfaces mediating protein-protein interactions are thought to be under strong evolutionary constraints, binding of the chemotaxis histidine kinase CheA to its phosphorylation target CheY...

Analysis of C5a-mediated chemotaxis by lentiviral delivery of small interfering RNA (2004)

Hwang, Jong-Ik, Fraser, Iain D. C., Choi, Sangdun, Qin, Xiao-Feng, Simon, Melvin I.

Immune cells respond to chemotactic signals by means of G protein-coupled receptors. Attempts to elucidate the function of specific G protein family members in these responses is complicated by...

Novel form of adaptation in mouse retinal rods speeds recovery of phototransduction (2003)

Krispel, Claudia M., Chen, Ching-Kang, Simon, Melvin I., Burns, Marie E.

Photoreceptors of the retina adapt to ambient light in a manner that allows them to detect changes in illumination over an enormous range of intensities. We have discovered a novel form of adaptation...

Thrombin Protease-activated Receptor-1 Signals through Gq- and G13-initiated MAPK Cascades Regulating c-Jun Expression to Induce Cell Transformation (2003)

Marinissen, Maria Julia, Servitja, Joan-Marc, Offermanns, Stefan, Simon, Melvin I., Gutkind, J. Silvio

Although the ability of G protein-coupled receptors to stimulate normal and aberrant cell growth has been intensely investigated, the precise nature of the molecular mechanisms underlying their...

A quantitative characterization of the yeast heterotrimeric G protein cycle (2003)

Yi, Tau-Mu, Kitano, Hiroaki, Simon, Melvin I.

The yeast mating response is one of the best understood heterotrimeric G protein signaling pathways. Yet, most descriptions of this system have been qualitative. We have quantitatively characterized...

Instability of GGL domain-containing RGS proteins in mice lacking the G protein β-subunit Gβ5 (2003)

Chen, Ching-Kang, Eversole-Cire, Pamela, Zhang, Haikun, Mancino, Valeria, Chen, Yu-Jiun, He, Wei, ...

RGS (regulator of G protein signaling) proteins containing the G protein gamma-like (GGL) domain (RGS6, RGS7, RGS9, and RGS11) interact with the fifth member of the G protein beta-subunit family,...

Orphan G protein-coupled receptors MrgA1 and MrgC11 are distinctively activated by RF-amide-related peptides through the G{alpha}q/11 pathway (2002)

Han, Sang-Kyou, Dong, Xinzhong, Hwang, Jong-Ik, Zylka, Mark J., Anderson, David J., Simon, Melvin I.

MrgA1 and MrgC11 belong to a recently identified family of orphan G-protein coupled receptors, called mrgs (mas-related genes). They are only expressed in a specific subset of sensory neurons that...

Interaction of G alpha(12) with G alpha(13) and G alpha(q) signaling pathways (2002)

Gu, Jennifer L., Müller, Stefan, Mancino, Valeria, Offermanns, Stefan, Simon, Melvin I.

The G(12) subfamily of heterotrimeric G-proteins consists of two members, G(12) and G(13). Gene-targeting studies have revealed a role for G(13) in blood vessel development. Mice lacking the a...

Genome sequence of the hyperthermophilic crenarchaeon Pyrobaculum aerophilum (2002)

Fitz-Gibbon, Sorel T., Ladner, Heidi, Kim, Ung-Jin, Stetter, Karl O., Simon, Melvin I., Miller, Jeffrey H.

We determined and annotated the complete 2.2-megabase genome sequence of Pyrobaculum aerophilum, a facultatively aerobic nitrate-reducing hyperthermophilic (T-opt = 100 degrees C) crenarchaeon. Clues...

Gene expression profiles of light-induced apoptosis in arrestin/rhodopsin kinase-deficient mouse retinas (2001)

Choi, Sangdun, Hao, Wenshan, Chen, Ching-Kang, Simon, Melvin I.

To examine the molecular processes that lead to light-induced retinal degeneration, mutant mice deficient in arrestin and rhodopsin kinase were raised in the dark and then subjected to relatively low...

Modules in the photoreceptor RGS9-1•Gβ5L GTPase-accelerating protein complex control effector coupling, GTPase acceleration, protein folding, and stability (2000)

He, Wei, Lu, Lisha, Zhang, Xue, El-Hodiri, Heithem M., Chen, Ching-Kang, Slep, Kevin C., ...

RGS (regulators of G protein signaling proteins regulate G protein signaling by accelerating GTP hydrolysis, but little is known about regulation of GTPase-accelerating protein (GAP) activities or...

Direct genetic demonstration of Galpha 13 coupling to the orphan G protein-coupled receptor G2A leading to RhoA-dependent actin rearrangement (2000)

Kabarowski, Janusz H. S., Feramisco, Jamison D., Le, Lu Q., Gu, Jennifer L., Luoh, Shiuh-Wen, Simon, Melvin I., ...

G2A is an orphan G protein-coupled receptor (GPCR), expressed predominantly in T and B cells and homologous to a small group of GPCRs of unknown function expressed in lymphoid tissues. G2A is...

Molecular Mechanism of the Inhibition of Phospholipase C β3 by Protein Kinase C (2000)

Yue, Caiping, Ku, Chun-Ying, Liu, Mingyao, Simon, Melvin I., Sanborn, Barbara M.

Activation of protein kinase C (PKC) can result from stimulation of the receptor-G protein-phospholipase C (PLCβ) pathway. In turn, phosphorylation of PLCβ by PKC may play a role in the regulation...

Polarity Exchange at the Interface of Regulators of G Protein Signaling with G Protein α-Subunits (2000)

Wieland, Thomas, Bahitjari, Nehat, Zhou, Xiao-Bo, Kleuss, Christiane, Simon, Melvin I.

RGS proteins are GTPase-activating proteins (GAPs) for G protein alpha -subunits. This GAP activity is mediated by the interaction of conserved residues on regulator of G protein signaling (RGS)...

Robust perfect adaptation in bacterial chemotaxis through integral feedback control (2000)

Yi, Tau-Mu, Huang, Yun, Simon, Melvin I., Doyle, John

Integral feedback control is a basic engineering strategy for ensuring that the output of a system robustly tracks its desired value independent of noise or variations in system parameters. In...

Co-expression of Gbeta 5 Enhances the Function of Two Ggamma Subunit-like Domain-containing Regulators of G Protein Signaling Proteins (2000)

Kovoor, Abraham, Chen, Ching-Kang, He, Wei, Wensel, Theodore G., Simon, Melvin I., Lester, Henry A.

Regulators of G protein signaling (RGS) stimulate the GTPase activity of G protein Galpha subunits and probably play additional roles. Some RGS proteins contain a Ggamma subunit-like (GGL) domain,...

Inhibition of Subsets of G Protein-coupled Receptors by Empty Mutants of G Protein α Subunits in Go, G11, and G16 (2000)

Yu, Bo, Gu, Lingjie, Simon, Melvin I.

We previously reported that the xanthine nucleotide binding Goα mutant, GoαX, inhibited the activation of Gi-coupled receptors. We constructed similar mutations in G11α and G16α and characterized...

Biopolymers: Protein and Nucleic Acids (2000)

Richards, John H., Abelson, John N., Hood, Leroy E., Simon, Melvin I., Campbell, Judith L.

The work focuses on learning the principles that govern interactions between proteins and nucleic acids. With these principles as guides we are synthesizing peptides (of about 50 amino acids) that...

Genomic Characterization of the Human Heterotrimeric G Protein {alpha}, {beta}, and {gamma} Subunit Genes (2000)

Hurowitz, Evan H., Melnyk, James M., Chen, Yu-Jiun, Kouros-Mehr, Hosein, Simon, Melvin I., Shizuya, Hiroaki

Heterotrimeric guanine nucleotide binding proteins (G proteins) transduce extracellular signals received by transmembrane receptors to effector proteins. Each subunit of the G protein complex is...

Abnormal photoresponses and light-induced apoptosis in rods lacking rhodopsin kinase (1999)

Chen, Ching-Kang, Burns, Marie E., Spencer, Maribeth, Niemi, Gregory A., Chen, Jeannie, Hurley, James B., ...

Phosphorylation is thought to be an essential first step in the prompt deactivation of photoexcited rhodopsin. In vitro, the phosphorylation can be catalyzed either by rhodopsin kinase (RK) or by...

Activation of G(12)/G(13) results in shape change and Rho/Rho-kinase-mediated myosin light chain phosphorylation in mouse platelets (1999)

Klages, Birgit, Brandt, Ursula, Simon, Melvin I., Schultz, Günter, Offermanns, Stefan

Platelets respond to various stimuli with rapid changes in shape followed by aggregation and secretion of their granule contents. Platelets lacking the alpha-subunit of the heterotrimeric G protein...

Phospholipase Cbeta 4 is specifically involved in climbing fiber synapse elimination in the developing cerebellum (1998)

Kano, Masanobu, Hashimoto, Kouichi, Watanabe, Masahiko, Kurihara, Hideo, Offermanns, Stefan, Jiang, Huiping, ...

Elimination of excess climbing fiber (CF)-Purkinje cell synapses during cerebellar development involves a signaling pathway that includes type 1 metabotropic glutamate receptor, Galpha q, and the...

Interaction of the Xanthine Nucleotide Binding Goα Mutant with G Protein-coupled Receptors (1998)

Yu, Bo, Simon, Melvin I.

We constructed a double mutant version of the α subunit of Go that was regulated by xanthine nucleotides instead of guanine nucleotides (GoαX). We investigated the interaction between GoαX and G...

Biopolymers: Protein and Nucleic Acids. (1998)

Richards, John H., Abelson, John N., Dervan, Peter B., Hood, Lee H., Simon, Melvin I.

The work focuses on learning the principles that govern interactions between proteins and nucleic acids both DNA and RNA (specifically tRNA). With these principles as guides we are synthesizing...

Bipolymers: Proteins and Nucleic Acids. (1998)

Richards, John J., Abelson, John N., Dervan, Peter B., Hood, Leroy H., Simon, Melvin I.

The scientific work supported by N00014-86-K-0755 focused on the basis of information content in macromolecules and how this information directs various biological processes. Specifically we dealt...

Biopolymers: Proteins and Nucleic Acids. (1998)

Richards, John H., Abelson, John N., Dervan, Peter B., Hood, Leroy E., Simon, Melvin I.

Our work focuses on molecular recognition by biopolymers as a model for interactions between macromolecules in general. Specifically we are learning the rules that govern protein-nucleic acid (both...

Specific Involvement of G Proteins in Regulation of Serum Response Factor-mediated Gene Transcription by Different Receptors (1998)

Mao, Junhao, Yuan, Huidong, Xie, Wei, Simon, Melvin I., Wu, Dianqing

Regulation of serum response factor (SRF)-mediated gene transcription by G protein subunits and G protein-coupled receptors was investigated in transfected NIH3T3 cells and in a cell line that was...

COS1, a two-component histidine kinase that is involved in hyphal development in the opportunistic pathogen Candida albicans (1998)

Alex, Lisa A., Korch, Christopher, Selitrennikoff, Claude P., Simon, Melvin I.

Two-component histidine kinases recently have been found in eukaryotic organisms including fungi, slime molds, and plants. We describe the identification of a gene, COS1, from the opportunistic...

Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking Galpha q (1997)

Offermanns, Stefan, Hashimoto, Kouichi, Watanabe, Masahiko, Sun, William, Kurihara, Hideo, Thompson, Richard F., ...

Mice lacking the alpha -subunit of the heterotrimeric guanine nucleotide binding protein Gq (Galpha q) are viable but suffer from ataxia with typical signs of motor discoordination. The anatomy of...

Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking G alpha q (1997)

Offermanns, Stefan, Hashimoto, Kouichi, Watanabe, Masahiko, Sun, William, Kurihara, Hideo, Thompson, Richard F., ...

Mice lacking the alpha-subunit of the heterotrimeric guanine nucleotide binding protein G(q) (G alpha(q)) are viable but suffer from ataxia with typical signs of motor discoordination. The anatomy of...

Constitutively Active Galpha q and Galpha 13 Trigger Apoptosis through Different Pathways (1997)

Althoefer, Henning, Eversole-Cire, Pamela, Simon, Melvin I.

We investigated the effect of expression of constitutively active Galpha mutants on cell survival. Transfection of constitutively active Galphaq and Galpha13 in two different cell lines caused...

Roles of phospholipase C beta 2 in chemoattractant-elicited responses (1997)

Jiang, Huiping, Kuang, Yanan, Wu, Yanping, Xie, Wei, Simon, Melvin I., Wu, Dianqing

The physiological roles of phospholipase C (PLC) beta 2 in hematopoiesis, leukocyte function, and host defense against infection were investigated using a mouse line that lacks PLC beta 2. PLC beta 2...

Characterization of a Goα Mutant That Binds Xanthine Nucleotides (1997)

Yu, Bo, Slepak, Vladlen Z., Simon, Melvin I.

Several GTP binding proteins, including EF-Tu, Ypt1, rab-5, and FtsY, and adenylosuccinate synthetase have been reported to bind xanthine nucleotides when the conserved aspartate residue in the NKXD...

Desensitization of Inositol 1,4,5-Trisphosphate/Ca2+-induced Cl- Currents by Prolonged Activation of G Proteins in Xenopus Oocytes (1996)

Quick, Michael W., Lester, Henry A., Davidson, Norman, Simon, Melvin I., Aragay, Anna M.

Expression of G protein alpha subunits of the Gq family with various G protein-coupled receptors induces activation of an inositol 1,4,5-trisphosphate (IP3)/Ca2+-mediated Cl- conductance in Xenopus...

Phospholipase C beta 4 is involved in modulating the visual response in mice (1996)

Jiang, Huiping, Lyubarsky, Arkady, Dodd, Robert, Vardi, Noga, Pugh, Edward, Baylor, Denis, ...

Expression of G protein-regulated phospholipase C (PLC) beta 4 in the retina, lateral geniculate nucleus, and superior colliculus implies that PLC beta 4 may play a role in the mammalian visual...

RGS-r, a retinal specific RGS protein, binds an intermediate conformation of transducin and enhances recycling (1996)

Chen, Ching-Kang, Wieland, Thomas, Simon, Melvin I.

G proteins regulate intracellular signaling by coupling a cycle of guanine nucleotide binding and hydrolysis to transient changes of cellular functions. The mechanisms that control the recycling of...

In vivo and in vitro characterization of Escherichia coli protein CheZ gain- and loss-of-function mutants (1996)

Sanna, M. Germana, Simon, Melvin I.

Bacterial chemotaxis results from the ability of flagellated bacteria to control the frequency of switching between smooth-swimming and tumbling episodes in response to changes in concentration of...

Galpha 12 and Galpha 13 Are Phosphorylated during Platelet Activation (1996)

Offmanns, Stefan, Hu, Yi-Hui, Simon, Melvin I.

The ubiquitously expressed G-proteins G12 and G13 whose function is currently not clear have been shown to be activated in platelet membranes through receptors that stimulate platelet aggregation. We...

bcl-2 overexpression reduces apoptotic photoreceptor cell death in three different retinal degenerations (1996)

Chen, Jeannie, Flannery, John G., LaVail, Matthew M., Steinberg, Roy H., Xu, Jun, Simon, Melvin I.

Apoptosis of photoreceptors occurs infrequently in adult retina but can be triggered in inherited and environmentally induced retinal degenerations. The protooncogene bcl-2 is known to be a potent...

Archaeal ubiquity (1996)

Stein, Jeffrey L., Simon, Melvin I.

In the seventeenth century, Antoine von Leeuwenhook used a simple microscope to discover that we live within a previously undetected microbial world containing an enormously diverse population of...

A bacterial artificial chromosome-based framework contig map of human chromosome 22q (1996)

Kim, Ung-Jin, Shizuya, Hiroaki, Kang, Hyung-Lyun, Choi, Sun-Shim, Garrett, Charmain L., Smink, Luc J., ...

We have constructed a physical map of human chromosome 22q using bacterial artificial chromosome (BAC) clones. The map consists of 613 chromosome 22-specific BAC clones that have been localized and...

Pertussis Toxin-sensitive Activation of Phospholipase C by the C5a and fMet-Leu-Phe Receptors (1996)

Jiang, Huiping, Kuang, Yanan, Wu, Yanping, Smrcka, Alan, Simon, Melvin I., Wu, Dianqing

Signal transduction pathways that mediate C5a and fMet-Leu-Phe (fMLP)-induced pertussis toxin (PTx)-sensitive activation of phospholipase C (PLC) have been investigated using a cotransfection assay...

Hyphal development in Neurospora crassa: Involvement of a two-component histidine kinase (1996)

Alex, Lisa A., Borkovich, Katherine A., Simon, Melvin I.

Two-component signal transduction systems are most often found in prokaryotic organisms where they are responsible for mediating the cellular responses to many environmental stimuli. These systems...

Isolation and in vitro characterization of CheZ suppressors for the Escherichia coli chemotactic response regulator mutant CheYN23D (1996)

Sanna, M. Germana, Simon, Melvin I.

The phosphorylated form of the response regulator CheY promotes the tumble signal in Escherichia coli chemotaxis. Phospho-CheY is thought to interact with the switch at the base of the flagellar...

Thermostable chemotaxis proteins from the hyperthermophilic bacterium Thermotoga maritima (1996)

Swanson, Ronald V., Sanna, M. Germana, Simon, Melvin I.

An expressed sequence tag homologous to cheA was previously isolated by random sequencing of Thermotoga maritima cDNA clones (C. W. Kim, P. Markiewicz, J. J. Lee, C. F. Schierle, and J. H. Miller, J....

Desensitization of Inositol 1,4,5-Trisphosphate/Ca²+-induced CL- Currents by Prolonged Activation of G Proteins in Xenopus Oocytes (1996)

Xenopus Oocytes, Michael W. Quick, Henry A. Lester, Norman Davidson, Melvin I. Simon, Anna M. Aragay

this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate...

G12 Requirement for Thrombin-stimulated Gene Expression and DNA Synthesis in 1321N1 Astrocytoma Cells (1995)

Aragay, Anna M., Collins, Lila R., Post, Ginell R., Watson, A. John, Feramisco, James R., Brown, Joan Heller, ...

Thrombin stimulation of 1321N1 astrocytoma cells leads to Ras-dependent AP-1-mediated transcriptional activation and to DNA replication. In contrast to what has been observed in most cell systems, in...

Gα15 and Gα16 Couple a Wide Variety of Receptors to Phospholipase C (1995)

Offermanns, Stefan, Simon, Melvin I.

The murine G-protein α-subunit Gα15 and its human counterpart Gα16 are expressed in a subset of hematopoietic cells, and they have been shown to regulate β-isoforms of inositide-specific...

Functional Analysis of a Dominant Negative Mutant of Gαi2 (1995)

Slepak, Vladlen Z., Katz, Arieh, Simon, Melvin I.

The key event in receptor-catalyzed activation of heterotrimeric G proteins is binding of GTP, which leads to subunit dissociation generating GTP-bound alpha subunits and free beta complexes. We have...

Differential coupling of G protein alpha subunits to seven-helix receptors expressed in Xenopus oocytes (1994)

Quick, Michael W., Simon, Melvin I., Davidson, Norman, Lester, Henry A., Aragay, Anna M.

Xenopus oocytes were used to examine the coupling of the serotonin 1c (5HT1c) and thyrotropin-releasing hormone (TRH) receptors to both endogenous and heterologously expressed G protein alpha...

Activation of phospholipase C beta4 by heterotrimeric GTP-binding proteins (1994)

Jiang, Huiping, Wu, Dianqing, Simon, Melvin I.

Transient transfection assays were used to determine how the activity of phospholipase C beta 4, which is preferentially expressed in retina, was regulated. An expression vector carrying the...

Purification and characterization of recombinant G16 alpha from Sf9 cells: activation of purified phospholipase C isozymes by G-protein alpha subunits (1993)

Kozasa, Tohru, Hepler, John R., Smrcka, Alan V., Simon, Melvin I., Rhee, Sue Goo, Sternweis, Paul C., ...

A cDNA encoding G16 alpha, the alpha subunit of a heterotrimeric guanine nucleotide-binding protein, was expressed in Sf9 cells using recombinant baculovirus. G16 alpha in membrane extracts of Sf9...

Purification from Sf9 cells and characterization of recombinant Gq alpha and G11 alpha. Activation of purified phospholipase C isozymes by G alpha subunits (1993)

Hepler, John R., Kozasa, Tohru, Smrcka, Alan V., Simon, Melvin I., Rhee, Sue Goo, Sternweis, Paul C., ...

Members of the Gq alpha subfamily of heterotrimeric guanine nucleotide-binding proteins (G proteins) activate phospholipase C (PLC). The complementary DNAs (cDNAs) for the G protein alpha subunits Gq...

Activation of the phosphosignaling protein CheY. I. Analysis of the phosphorylated conformation by 19F NMR and protein engineering (1993)

Drake, Steven K., Bourret, Robert B., Luck, Linda A., Simon, Melvin I., Falke, Joseph J.

CheY, the 14-kDa response regulator protein of the Escherichia coli chemotaxis pathway, is activated by phosphorylation of Asp57. In order to probe the structural changes associated with activation,...

Activation of the phosphosignaling protein CheY. II. Analysis of activated mutants by 19F NMR and protein engineering (1993)

Bourret, Robert B., Drake, Steven K., Chervitz, Stephen A., Simon, Melvin I., Falke, Joseph J.

The Escherichia coli CheY protein is activated by phosphorylation, and in turn alters flagellar rotation. To investigate the molecular mechanism of activation, an extensive collection of mutant CheY...

Activation of phospholipase C beta 2 by the alpha and beta gamma subunits of trimeric GTP-binding protein (1993)

Wu, Dianqing, Katz, Arieh, Simon, Melvin I.

Cotransfection assays were used to show that the members of the GTP-binding protein Gq class of alpha subunits could activate phospholipase C (PLC) beta 2. Similar experiments also demonstrated that...

Computer simulation of the phosphorylation cascade controlling bacterial chemotaxis (1993)

Bray, Dennis, Bourret, Robert B., Simon, Melvin I.

We have developed a computer program that simulates the intracellular reactions mediating the rapid (nonadaptive) chemotactic response of Escherichia coli bacteria to the attractant aspartate and the...

The carboxy-terminal portion of the CheA kinase mediates regulation of autophosphorylation by transducer and CheW (1993)

Bourret, Robert B., Davagnino, Juan, Simon, Melvin I.

The CheA kinase is a central protein in the signal transduction network that controls chemotaxis in Escherichia coli. CheA receives information from a transmembrane receptor (e.g., Tar) and CheW...

The G alpha q and G alpha 11 proteins couple the thyrotropin-releasing hormone receptor to phospholipase C in GH3 rat pituitary cells (1992)

Aragay, Anna M., Katz, Arieh, Simon, Melvin I.

Thyrotropin-releasing hormone stimulates the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) in GH3 cell membranes. The stimulation of the phosphoinositide phospholipase C (PI/PLC)...

G protein beta gamma subunits synthesized in Sf9 cells. Functional characterization and the significance of prenylation of gamma (1992)

Iñiguez-Lluhi, Jorge A., Simon, Melvin I., Robishaw, Janet D., Gilman, Alfred G.

Heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins) consist of a nucleotide-binding alpha subunit and a high- affinity complex of beta and gamma subunits. There is molecular...

Attenuation of Sensory Receptor Signaling by Covalent Modification (1992)

Borkovich, Katherine A., Alex, Lisa A., Simon, Melvin I.

The Tar receptor is a transmembrane protein that regulates bacterial chemotaxis in response to changes in the level of aspartic acid in the medium. The extracellular portion of the protein can bind...

Retinal degeneration is rescued in transgenic rd mice by expression of the cGMP phosphodiesterase ß subunit (1992)

Lem, Janis, Flannery, John G., Li, Tiansen, Applebury, Meredithe L., Farber, Debora B., Simon, Melvin I.

The ß subunit of the cGMP phosphodiesterase (PDE) gene has been identified as the candidate gene for retinal degeneration in the rd mouse. To study the molecular mechanisms underlying degeneration...

Determination of transmembrane protein structure by disulfide cross-linking: The Escherichia coli Tar receptor (1992)

Pakula, Andrew A., Simon, Melvin I.

We have devised a generally applicable strategy for analysis of protein structure and have applied it to examine the structure of the transmembrane portion of the Tar receptor of Escherichia coli....

Stable propagation of cosmid sized human DNA inserts in an F factor based vector (1992)

Kim, Ung-Jin, Shizuya, Hiroaki, De Jong, Pieter J., Birren, Bruce, Simon, Melvin I.

Instability of complex mammalian genomic DNA inserts is commonplace in cosmid libraries constructed in conventional multicopy vectors. To develop a means to construct stable libraries, we have...

Stable propagation of cosmid sized human DNA inserts in an F factor based vector (1992)

Kim, Ung-Jin, Shizuya, Hiroaki, De Jong, Pieter J., Birren, Bruce, Simon, Melvin I.

Instability of complex mammalian genomic DNA inserts is commonplace in cosmid libraries constructed in conventional multicopy vectors. To develop a means to construct stable libraries, we have...

Gα16, a G Protein α Subunit Specifically Expressed in Hematopoietic Cells (1991)

Steele, David A., Slepak, Vladlen Z., Simon, Melvin I.

Signal-transduction pathways mediated by guanine nucleotide-binding regulatory proteins (G proteins) determine many of the responses of hematopoietic cells. A recently identified gene encoding a G...

Transposon-facilitated DNA sequencing (1991)

Strathmann, Michael, Hamilton, Bruce A., Mayeda, Carol A., Simon, Melvin I., Meyerowitz, Eliott M., Palazollo, Michael J.

We describe here a transposon-based DNA sequencing strategy that allows the introduction of sequencing priming sites throughout a target sequence by bacterial mating. A miniplasmid was designed to...

Homologous and unique G protein alpha subunits in the nematode Caenorhabditis elegans (1991)

Lochrie, Michael A., Mendel, Jane E., Sternberg, Paul W., Simon, Melvin I.

A cDNA corresponding to a known G protein alpha subunit, the alpha subunit of Go (Go alpha), was isolated and sequenced. The predicted amino acid sequence of C. elegans Go alpha is 80-87% identical...

Determining transcript number using the polymerase chain reaction: Pgk-2, mP2, and PGK-2 transgene mRNA levels during spermatogenesis (1991)

Robinson, Murray O., Simon, Melvin I.

We describe a technique that uses reverse transcription and the polymerase chain reaction (per) to rapidly quantitate numbers of specific mRNA transcripts from nanogram quantities of total cellular...

G protein diversity: a distinct class of α subunits is present in vertebrates and invertebrates (1990)

Strathmann, Michael, Simon, Melvin I.

Heterotrimeric guanine nucleotide-binding proteins (G proteins) are integral to the signal transduction pathways that mediate the cell's response to many hormones, neuromodulators, and a variety of...

G protein diversity is increased by associations with a variety of gamma subunits (1990)

Gautam, Narasimha, Northup, John, Tamir, Haya, Simon, Melvin I.

Guanine nucleotide-binding regulatory proteins (G proteins) are heterotrimeric proteins that transduce extracellular signals into intracellular changes. Functionally different G proteins have been...

Gz, a guanine nucleotide-binding protein with unique biochemical properties (1990)

Casey, Patrick J., Fong, Henry K. W., Simon, Melvin I., Gilman, Alfred G.

Cloning of a complementary DNA (cDNA) for Gz alpha, a newly appreciated member of the family of guanine nucleotide-binding regulatory proteins (G proteins), has allowed preparation of specific...

Conserved Aspartate Residues and Phosphorylation in Signal Transduction by the Chemotaxis Protein CheY (1990)

Bourret, Robert B., Hess, J. Fred, Simon, Melvin I.

The CheY protein is phosphorylated by CheA and dephosphorylated by CheZ as part of the chemotactic signal transduction pathway in Escherichia coli. Phosphorylation of CheY has been proposed to occur...

Conserved aspartate residues and phosphorylation in signal transduction by the chemotaxis protein CheY (1990)

Bourret, Robert B., Hess, J. Fred, Simon, Melvin I.

The CheY protein is phosphorylated by CheA and dephosphorylated by CheZ as part of the chemotactic signal transduction pathway in Escherichia coli. Phosphorylation of CheY has been proposed to occur...

The basis of high resolution separation of small DNAs by asymmetric-voltage field inversion electrophoresis and its application to DNA sequencing gels (1990)

Birrer, Bruce W., Simon, Melvin I., Lai, Eric

We have previously shown that asymmetric-voltage field inversion electrophoresis produces more uniform separation for fragments between 1 and 50 kilobases (kb) than other modes of pulsed field gel...

Transcriptional regulatory regions of testis-specific PGK2 defined in transgenic mice (1989)

Robinson, Murray O., McCarrey, John R., Simon, Melvin I.

The gene encoding testis-specific phosphoglycerate kinase 2 (PGK; ATP:3-phospho-D-glycerate 1-phosphotransferase, EC 2.7.2.3) is expressed only in meiotic and haploid male germ cells. Transgenic mice...

Transmembrane Signal Transduction in Bacterial Chemotaxis Involves Ligand-Dependent Activation of Phosphate Group Transfer (1989)

Borkovich, Katherine A., Kaplan, Nachum, Hess, J. Fred, Simon, Melvin I.

Signal transduction in Escherichia coli involves the interaction of transmembrane receptor proteins such as the aspartate receptor, Tar, and the products of four chemotaxis genes, cheA, cheY, cheW,...

Purification and characterization of the wild-type and mutant carboxy-terminal domains of the Escherichia coli Tar chemoreceptor (1988)

Kaplan, Nachum, Simon, Melvin I.

The carboxy-terminal half of the Escherichia coli Tar chemoreceptor protein was cloned into an overproducing plasmid with the transcription of the insert under the control of the strong hybrid tac...

Isolation of the Gene Encoding the Hin Recombinational Enhancer Binding Protein (1988)

Johnson, Reid C., Ball, Catherine A., Pfeffer, Diana, Simon, Melvin I.

In vitro DNA inversion mediated by the protein Hin requires the presence of a recombinational enhancer sequence located in cis relative to the recombination sites and a protein, Fis, which binds to...

Identification of a GTP-binding protein alpha subunit that lacks an apparent ADP-ribosylation site for pertussis toxin (1988)

Fong, Henry K. W., Yoshimoto, Kenneth K., Eversole-Cire, Pamela, Simon, Melvin I.

Recent molecular cloning of cDNA for the alpha subunit of bovine transducin (a guanine nucleotide-binding regulatory protein, or G protein) has revealed the presence of two retinal-specific...

Optimized conditions for pulsed field gel electrophoretic separations of DNA (1988)

Birren, Bnice W., Lai, Eric, Clark, Steven M., Hood, Leroy, Simon, Melvin I.

Quantitative measurement of DNA migration in gel electrophoresis requires precisely controlled homogeneous electric fields. A new electrophoresis system has allowed us to explore several parameters...

Protein phosphorylation is involved in bacterial chemotaxis (1987)

Hess, J. Fred, Oosawa, Kenji, Matsumura, Philip, Simon, Melvin I.

The nature of the biochemical signal that is involved in the excitation response in bacterial chemotaxis is not known. However, ATP is required for chemotaxis. We have purified all of the proteins...

Distinct forms of the ß subunit of GTP-binding regulatory proteins identified by molecular cloning (1987)

Fong, Henry K. W., Birren, Bruce W., Simon, Melvin I.

Two distinct β subunits of guanine nucleotide-binding regulatory proteins have been identified by cDNA cloning and are referred to as β 1 and β 2 subunits. The bovine transducin β subunit (β 1)...

Characterization of Escherichia coli chemotaxis receptor mutants with null phenotypes (1986)

Mutoh, Norihiro, Oosawa, Kenji, Simon, Melvin I.

Hydroxylamine mutagenesis was used to alter the tar gene that encodes the transmembrane Tar protein required for chemotaxis. Mutants defective in chemotaxis were selected, and the mutation was...

Repetitive Segmental Structure of the Transducin β Subunit: Homology with the CDC4 Gene and Identification of Related mRNAs (1986)

Fong, Henry K. W., Hurley, James B., Hopkins, Rosemary S., Miake-Lye, Ryn, Johnson, Mark S., Doolittle, Russell F., ...

Retinal transducin, a guanine nucleotide regulatory protein (referred to as a G protein) that activates a cGMP phosphodiesterase in photoreceptor cells, is comprised of three subunits. We have...

Nucleotide sequence corresponding to five chemotaxis genes in Escherichia coli (1986)

Mutoh, Norihiro, Simon, Melvin I.

The nucleotide sequence of DNA which contains five chemotaxis-related genes of Escherichia coli, cheW, cheR, cheB, cheY, and cheZ, and part of the cheA gene was determined. Molecular weights of the...

Evolution and Organization of the Fibrinogen Locus on Chromosome 4: Gene Duplication Accompanied by Transposition and Inversion (1985)

Kant, Jeffrey A., Saxe, Debra, Simon, Melvin I., McBride, O. Wesley, Crabtree, Gerald R.

Human fibrinogen cDNA probes for the alpha-, beta-, and gamma-polypeptide chains have been used to isolate the corresponding genes from human genomic libraries. There is a single copy of each gene....

Nucleotide sequence of the luxA gene of Vibrio harveyi and the complete amino acid sequence of the alpha subunit of bacterial luciferase (1985)

Cohn, Daniel H., Mileham, Alan J., Simon, Melvin I., Nealson, Kenneth H., Rausch, Steven K., Bonam, Duane, ...

The nucleotide sequence of the 1.85-kilobase EcoRI fragment from Vibrio harveyi that was cloned using a mixed-sequence synthetic oligonucleotide probe (Cohn, D. H., Ogden, R. C., Abelson, J. N.,...

Chimeric chemosensory transducers of Escherichia coli (1985)

Krikos, Alexandra, Conley, M. Patricia, Boyd, Alan, Berg, Howard C., Simon, Melvin I.

The tar and tsr genes of Escherichia coli encode homologous transducer proteins that mediate distinct chemotactic responses. We report here the construction of two tasr chimeric genes in which the 5'...

Isolation and Characterization of a cDNA Clone for the gamma Subunit of Bovine Retinal Transducin (1984)

Hurley, James B., Fong, Henry K. W., Teplow, David B., Dreyer, William J., Simon, Melvin I.

We have isolated and characterized a cDNA clone that encodes the gamma subunit of transducin, the guanine nucleotide binding regulatory protein found in vertebrate photoreceptors. The gamma subunit...

Phase variation and the Hin protein: in vivo activity measurements, protein overproduction, and purification (1984)

Bruist, Michael F., Simon, Melvin I.

The alternate expression of the Salmonella flagellin genes H1 and H2 is controlled by the orientation of a 995-base-pair invertible segment of DNA located at the 5' end of the H2 gene. The hin gene,...

Chromosomal mapping of the mink cell focus-inducing and xenotropic env gene family in the mouse (1983)

Blatt, Cila, Mileham, Karen, Haas, Martin, Nesbitt, Muriel N., Harper, Mary E., Simon, Melvin I.

Chromosomal locations of members of the xenotropic-related env gene family in the mouse genome have been determined. Endonuclease restriction site polymorphisms detected by molecular hybridization...

Cloning of the Vibrio harveyi luciferase genes: use of a synthetic oligonucleotide probe (1983)

Cohn, Daniel H., Ogden, Richard C., Abelson, John N., Baldwin, Thomas O., Nealson, Kenneth H., Simon, Melvin I., ...

A mixed-sequence synthetic oligonucleotide probe was used to isolate a clone containing the gene encoding the alpha subunit of bacterial luciferase from Vibrio harveyi and part of the gene coding for...

Diphtheria toxin forms transmembrane channels in planar lipid bilayers (1981)

Donovan, James J., Simon, Melvin I., Draper, Rockford K., Montal, Mauricio

When exposed to a lipid bilayer, diphtheria toxin binds to it and forms transmembrane, voltage-dependent, anion-selective channels. The mean (± SD) conductance of these channels in asolectin...

The entry of diphtheria toxin into the mammalian cell cytoplasm: evidence for lysosomal involvement (1980)

Draper, Rockford K., Simon, Melvin I.

Lysosomotropic amines, such as ammonium chloride, are known to protect cells from the cytotoxic effects of diphtheria toxin. These drugs are believed to inhibit the transport of the toxin from a...

Multiple electrophoretic forms of methyl-accepting chemotaxis proteins generated by stimulus-elicited methylation in Escherichia coli (1980)

Boyd, Alan, Simon, Melvin I.

The tsr and tar genetic loci of Escherichia coli determine the presence in sodium dodecyl sulfate-polyacrylamide gel electrophoresis of methyl-accepting chemotaxis proteins (MCPs) I and II,...

Diphtheria toxin has the properties of a lectin (1978)

Draper, Rockford K., Chin, Daniel, Simon, Melvin I.

The inhibition of protein synthesis in Chinese hamster V79 cells by diphtheria toxin is antagonized by the lectins concanavalin A, succinylated concanavalin A, and wheat germ agglutinin but not by...

Variation in the Primary Structure of Bacillus subtilis Flagellins (1971)

Emerson, Suzanne U., Simon, Melvin I.

The flagella derived from 18 strains Bacillus subtilis were tested for their reaction with antiflagellar filament antibody and antiflagellin antibody. On the basis of their reactivity, at least five...

Direct genetic demonstration of Gα13 coupling to the orphan G protein-coupled receptor G2A leading to RhoA-dependent actin rearrangement

Kabarowski, Janusz H. S., Feramisco, Jamison D., Le, Lu Q., Gu, Jennifer L., Luoh, Shiuh-Wen, Simon, Melvin I., ...

G2A is an orphan G protein-coupled receptor (GPCR), expressed predominantly in T and B cells and homologous to a small group of GPCRs of unknown function expressed in lymphoid tissues. G2A is...

Robust perfect adaptation in bacterial chemotaxis through integral feedback control

Yi, Tau-Mu, Huang, Yun, Simon, Melvin I., Doyle, John

Integral feedback control is a basic engineering strategy for ensuring that the output of a system robustly tracks its desired value independent of noise or variations in system parameters. In...

Roles of phospholipase C β2 in chemoattractant-elicited responses

Jiang, Huiping, Kuang, Yanan, Wu, Yanping, Xie, Wei, Simon, Melvin I., Wu, Dianqing

The physiological roles of phospholipase C (PLC) β2 in hematopoiesis, leukocyte function, and host defense against infection were investigated using a mouse line that lacks PLC β2. PLC β2...

Abnormal photoresponses and light-induced apoptosis in rods lacking rhodopsin kinase

Chen, Ching-Kang, Burns, Marie E., Spencer, Maribeth, Niemi, Gregory A., Chen, Jeannie, Hurley, James B., ...

Phosphorylation is thought to be an essential first step in the prompt deactivation of photoexcited rhodopsin. In vitro, the phosphorylation can be catalyzed either by rhodopsin kinase (RK) or by...

COS1, a two-component histidine kinase that is involved in hyphal development in the opportunistic pathogen Candida albicans

Alex, Lisa A., Korch, Christopher, Selitrennikoff, Claude P., Simon, Melvin I.

Two-component histidine kinases recently have been found in eukaryotic organisms including fungi, slime molds, and plants. We describe the identification of a gene, COS1, from the opportunistic...

Phospholipase Cβ4 is specifically involved in climbing fiber synapse elimination in the developing cerebellum

Kano, Masanobu, Hashimoto, Kouichi, Watanabe, Masahiko, Kurihara, Hideo, Offermanns, Stefan, Jiang, Huiping, ...

Elimination of excess climbing fiber (CF)–Purkinje cell synapses during cerebellar development involves a signaling pathway that includes type 1 metabotropic glutamate receptor, Gαq, and the γ...

Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking Gαq

Offermanns, Stefan, Hashimoto, Kouichi, Watanabe, Masahiko, Sun, William, Kurihara, Hideo, Thompson, Richard F., ...

Mice lacking the α-subunit of the heterotrimeric guanine nucleotide binding protein Gq (Gαq) are viable but suffer from ataxia with typical signs of motor discoordination. The anatomy of the...

Gene expression profiles of light-induced apoptosis in arrestin/rhodopsin kinase-deficient mouse retinas

Choi, Sangdun, Hao, Wenshan, Chen, Ching-Kang, Simon, Melvin I.

To examine the molecular processes that lead to light-induced retinal degeneration, mutant mice deficient in arrestin and rhodopsin kinase were raised in the dark and then subjected to relatively low...

Genome sequence of the hyperthermophilic crenarchaeon Pyrobaculum aerophilum

Fitz-Gibbon, Sorel T., Ladner, Heidi, Kim, Ung-Jin, Stetter, Karl O., Simon, Melvin I., Miller, Jeffrey H.

We determined and annotated the complete 2.2-megabase genome sequence of Pyrobaculum aerophilum, a facultatively aerobic nitrate-reducing hyperthermophilic (Topt = 100°C) crenarchaeon. Clues were...

Interaction of Gα12 with Gα13 and Gαq signaling pathways

Gu, Jennifer L., Müller, Stefan, Mancino, Valeria, Offermanns, Stefan, Simon, Melvin I.

The G12 subfamily of heterotrimeric G-proteins consists of two members, G12 and G13. Gene-targeting studies have revealed a role for G13 in blood vessel development. Mice lacking the α subunit of...

Orphan G protein-coupled receptors MrgA1 and MrgC11 are distinctively activated by RF-amide-related peptides through the Gαq/11 pathway

Han, Sang-Kyou, Dong, Xinzhong, Hwang, Jong-Ik, Zylka, Mark J., Anderson, David J., Simon, Melvin I.

MrgA1 and MrgC11 belong to a recently identified family of orphan G-protein coupled receptors, called mrgs (mas-related genes). They are only expressed in a specific subset of sensory neurons that...

Instability of GGL domain-containing RGS proteins in mice lacking the G protein β-subunit Gβ5

Chen, Ching-Kang, Eversole-Cire, Pamela, Zhang, Haikun, Mancino, Valeria, Chen, Yu-Jiun, He, Wei, ...

RGS (regulator of G protein signaling) proteins containing the G protein γ-like (GGL) domain (RGS6, RGS7, RGS9, and RGS11) interact with the fifth member of the G protein β-subunit family, Gβ5....

A quantitative characterization of the yeast heterotrimeric G protein cycle

Yi, Tau-Mu, Kitano, Hiroaki, Simon, Melvin I.

The yeast mating response is one of the best understood heterotrimeric G protein signaling pathways. Yet, most descriptions of this system have been qualitative. We have quantitatively characterized...

Variation in the Primary Structure of Bacillus subtilis Flagellins1

Emerson, Suzanne U., Simon, Melvin I.

The flagella derived from 18 strains Bacillus subtilis were tested for their reaction with antiflagellar filament antibody and antiflagellin antibody. On the basis of their reactivity, at least five...

Synthesis of Bacterial Flagella II. PBSl Transduction of Flagella-specific Markers in Bacillus subtilis

Grant, Geoffrey F., Simon, Melvin I.

The linkage relationship of mutants involved in the synthesis of flagella was determined by PBSl transduction. Mutants that affect the structure of flagellin (hag) and temperature-sensitive mutants...

Flagellar Assembly Mutants in Escherichia coli1

Silverman, Michael R., Simon, Melvin I.

Genetic and biochemical analysis of mutants defective in the synthesis of flagella in Escherichia coli revealed an unusual class of mutants. These mutants were found to produce short, curly,...

A 12-Mb Complete Coverage BAC Contig Map in Human Chromosome 16p13.1–p11.2

Cao, Yicheng, Kang, Hyung Lyun, Xu, Xuequn, Wang, Mei, Dho, So Hee, Huh, Jun Ryul, ...

We have constructed a complete coverage BAC contig map that spans a 12-Mb genomic segment in the human chromosome 16p13.1–p11.2 region. The map consists of 68 previously mapped STSs and 289 BAC...

Human Genome Anatomy: BACs Integrating the Genetic and Cytogenetic Maps for Bridging Genome and Biomedicine

Korenberg, Julie R., Chen, Xiao-Ning, Sun, Zhiguang, Shi, Zheng-Yang, Ma, Shaowu, Vataru, Eddy, ...

Human genome sequencing is accelerating rapidly. Multiple genome maps link this sequence to problems in biology and clinical medicine. Because each map represents a different aspect of the structure,...

Analysis of C5a-mediated chemotaxis by lentiviral delivery of small interfering RNA

Hwang, Jong-Ik, Fraser, Iain D. C., Choi, Sangdun, Qin, Xiao-Feng, Simon, Melvin I.

Immune cells respond to chemotactic signals by means of G protein-coupled receptors. Attempts to elucidate the function of specific G protein family members in these responses is complicated by...

In different organisms, the mode of interaction between two signaling proteins is not necessarily conserved

Park, Sang-Youn, Beel, Bryan D., Simon, Melvin I., Bilwes, Alexandrine M., Crane, Brian R.

Although interfaces mediating protein–protein interactions are thought to be under strong evolutionary constraints, binding of the chemotaxis histidine kinase CheA to its phosphorylation target...

Silencing the expression of multiple Gβ-subunits eliminates signaling mediated by all four families of G proteins

Hwang, Jong-Ik, Choi, Sangdun, Fraser, Iain D. C., Chang, Mi Sook, Simon, Melvin I.

The Gβγ-subunit complex derived from heterotrimeric G proteins can act to regulate the function of a variety of protein targets. We established lentiviral-based RNA interference in J774A.1 mouse...

Caenorhabditis elegans Galphaq regulates egg-laying behavior via a PLCbeta-independent and serotonin-dependent signaling pathway and likely functions both in the nervous system and in muscle.

Bastiani, Carol A, Gharib, Shahla, Simon, Melvin I, Sternberg, Paul W

egl-30 encodes the single C. elegans ortholog of vertebrate Galphaq family members. We analyzed the expression pattern of EGL-30 and found that it is broadly expressed, with highest expression in the...

Direct genetic demonstration of Gα13 coupling to the orphan G protein-coupled receptor G2A leading to RhoA-dependent actin rearrangement

Kabarowski, Janusz H. S., Feramisco, Jamison D., Le, Lu Q., Gu, Jennifer L., Luoh, Shiuh-Wen, Simon, Melvin I., ...

G2A is an orphan G protein-coupled receptor (GPCR), expressed predominantly in T and B cells and homologous to a small group of GPCRs of unknown function expressed in lymphoid tissues. G2A is...

Robust perfect adaptation in bacterial chemotaxis through integral feedback control

Yi, Tau-Mu, Huang, Yun, Simon, Melvin I., Doyle, John

Integral feedback control is a basic engineering strategy for ensuring that the output of a system robustly tracks its desired value independent of noise or variations in system parameters. In...

Roles of phospholipase C β2 in chemoattractant-elicited responses

Jiang, Huiping, Kuang, Yanan, Wu, Yanping, Xie, Wei, Simon, Melvin I., Wu, Dianqing

The physiological roles of phospholipase C (PLC) β2 in hematopoiesis, leukocyte function, and host defense against infection were investigated using a mouse line that lacks PLC β2. PLC β2...

Abnormal photoresponses and light-induced apoptosis in rods lacking rhodopsin kinase

Chen, Ching-Kang, Burns, Marie E., Spencer, Maribeth, Niemi, Gregory A., Chen, Jeannie, Hurley, James B., ...

Phosphorylation is thought to be an essential first step in the prompt deactivation of photoexcited rhodopsin. In vitro, the phosphorylation can be catalyzed either by rhodopsin kinase (RK) or by...

COS1, a two-component histidine kinase that is involved in hyphal development in the opportunistic pathogen Candida albicans

Alex, Lisa A., Korch, Christopher, Selitrennikoff, Claude P., Simon, Melvin I.

Two-component histidine kinases recently have been found in eukaryotic organisms including fungi, slime molds, and plants. We describe the identification of a gene, COS1, from the opportunistic...

Phospholipase Cβ4 is specifically involved in climbing fiber synapse elimination in the developing cerebellum

Kano, Masanobu, Hashimoto, Kouichi, Watanabe, Masahiko, Kurihara, Hideo, Offermanns, Stefan, Jiang, Huiping, ...

Elimination of excess climbing fiber (CF)–Purkinje cell synapses during cerebellar development involves a signaling pathway that includes type 1 metabotropic glutamate receptor, Gαq, and the γ...

Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking Gαq

Offermanns, Stefan, Hashimoto, Kouichi, Watanabe, Masahiko, Sun, William, Kurihara, Hideo, Thompson, Richard F., ...

Mice lacking the α-subunit of the heterotrimeric guanine nucleotide binding protein Gq (Gαq) are viable but suffer from ataxia with typical signs of motor discoordination. The anatomy of the...

Gene expression profiles of light-induced apoptosis in arrestin/rhodopsin kinase-deficient mouse retinas

Choi, Sangdun, Hao, Wenshan, Chen, Ching-Kang, Simon, Melvin I.

To examine the molecular processes that lead to light-induced retinal degeneration, mutant mice deficient in arrestin and rhodopsin kinase were raised in the dark and then subjected to relatively low...

Genome sequence of the hyperthermophilic crenarchaeon Pyrobaculum aerophilum

Fitz-Gibbon, Sorel T., Ladner, Heidi, Kim, Ung-Jin, Stetter, Karl O., Simon, Melvin I., Miller, Jeffrey H.

We determined and annotated the complete 2.2-megabase genome sequence of Pyrobaculum aerophilum, a facultatively aerobic nitrate-reducing hyperthermophilic (Topt = 100°C) crenarchaeon. Clues were...

Interaction of Gα12 with Gα13 and Gαq signaling pathways

Gu, Jennifer L., Müller, Stefan, Mancino, Valeria, Offermanns, Stefan, Simon, Melvin I.

The G12 subfamily of heterotrimeric G-proteins consists of two members, G12 and G13. Gene-targeting studies have revealed a role for G13 in blood vessel development. Mice lacking the α subunit of...

Orphan G protein-coupled receptors MrgA1 and MrgC11 are distinctively activated by RF-amide-related peptides through the Gαq/11 pathway

Han, Sang-Kyou, Dong, Xinzhong, Hwang, Jong-Ik, Zylka, Mark J., Anderson, David J., Simon, Melvin I.

MrgA1 and MrgC11 belong to a recently identified family of orphan G-protein coupled receptors, called mrgs (mas-related genes). They are only expressed in a specific subset of sensory neurons that...

Instability of GGL domain-containing RGS proteins in mice lacking the G protein β-subunit Gβ5

Chen, Ching-Kang, Eversole-Cire, Pamela, Zhang, Haikun, Mancino, Valeria, Chen, Yu-Jiun, He, Wei, ...

RGS (regulator of G protein signaling) proteins containing the G protein γ-like (GGL) domain (RGS6, RGS7, RGS9, and RGS11) interact with the fifth member of the G protein β-subunit family, Gβ5....

A quantitative characterization of the yeast heterotrimeric G protein cycle

Yi, Tau-Mu, Kitano, Hiroaki, Simon, Melvin I.

The yeast mating response is one of the best understood heterotrimeric G protein signaling pathways. Yet, most descriptions of this system have been qualitative. We have quantitatively characterized...

Variation in the Primary Structure of Bacillus subtilis Flagellins1

Emerson, Suzanne U., Simon, Melvin I.

The flagella derived from 18 strains Bacillus subtilis were tested for their reaction with antiflagellar filament antibody and antiflagellin antibody. On the basis of their reactivity, at least five...

Synthesis of Bacterial Flagella II. PBSl Transduction of Flagella-specific Markers in Bacillus subtilis

Grant, Geoffrey F., Simon, Melvin I.

The linkage relationship of mutants involved in the synthesis of flagella was determined by PBSl transduction. Mutants that affect the structure of flagellin (hag) and temperature-sensitive mutants...

Flagellar Assembly Mutants in Escherichia coli1

Silverman, Michael R., Simon, Melvin I.

Genetic and biochemical analysis of mutants defective in the synthesis of flagella in Escherichia coli revealed an unusual class of mutants. These mutants were found to produce short, curly,...

A 12-Mb Complete Coverage BAC Contig Map in Human Chromosome 16p13.1–p11.2

Cao, Yicheng, Kang, Hyung Lyun, Xu, Xuequn, Wang, Mei, Dho, So Hee, Huh, Jun Ryul, ...

We have constructed a complete coverage BAC contig map that spans a 12-Mb genomic segment in the human chromosome 16p13.1–p11.2 region. The map consists of 68 previously mapped STSs and 289 BAC...

Human Genome Anatomy: BACs Integrating the Genetic and Cytogenetic Maps for Bridging Genome and Biomedicine

Korenberg, Julie R., Chen, Xiao-Ning, Sun, Zhiguang, Shi, Zheng-Yang, Ma, Shaowu, Vataru, Eddy, ...

Human genome sequencing is accelerating rapidly. Multiple genome maps link this sequence to problems in biology and clinical medicine. Because each map represents a different aspect of the structure,...

Analysis of C5a-mediated chemotaxis by lentiviral delivery of small interfering RNA

Hwang, Jong-Ik, Fraser, Iain D. C., Choi, Sangdun, Qin, Xiao-Feng, Simon, Melvin I.

Immune cells respond to chemotactic signals by means of G protein-coupled receptors. Attempts to elucidate the function of specific G protein family members in these responses is complicated by...

In different organisms, the mode of interaction between two signaling proteins is not necessarily conserved

Park, Sang-Youn, Beel, Bryan D., Simon, Melvin I., Bilwes, Alexandrine M., Crane, Brian R.

Although interfaces mediating protein–protein interactions are thought to be under strong evolutionary constraints, binding of the chemotaxis histidine kinase CheA to its phosphorylation target...

Silencing the expression of multiple Gβ-subunits eliminates signaling mediated by all four families of G proteins

Hwang, Jong-Ik, Choi, Sangdun, Fraser, Iain D. C., Chang, Mi Sook, Simon, Melvin I.

The Gβγ-subunit complex derived from heterotrimeric G proteins can act to regulate the function of a variety of protein targets. We established lentiviral-based RNA interference in J774A.1 mouse...

Caenorhabditis elegans Galphaq regulates egg-laying behavior via a PLCbeta-independent and serotonin-dependent signaling pathway and likely functions both in the nervous system and in muscle.

Bastiani, Carol A, Gharib, Shahla, Simon, Melvin I, Sternberg, Paul W

egl-30 encodes the single C. elegans ortholog of vertebrate Galphaq family members. We analyzed the expression pattern of EGL-30 and found that it is broadly expressed, with highest expression in the...

A single lentiviral vector platform for microRNA-based conditional RNA interference and coordinated transgene expression

Shin, Kum-Joo, Wall, Estelle A., Zavzavadjian, Joelle R., Santat, Leah A., Liu, Jamie, Hwang, Jong-Ik, ...

RNAi is proving to be a powerful experimental tool for the functional annotation of mammalian genomes. The full potential of this technology will be realized through development of approaches...

Gαi2-mediated signaling events in the endothelium are involved in controlling leukocyte extravasation

Pero, Ralph S., Borchers, Michael T., Spicher, Karsten, Ochkur, Sergei I., Sikora, Lyudmila, Rao, Savita P., ...

The trafficking of leukocytes from the blood to sites of inflammation is the cumulative result of receptor-ligand-mediated signaling events associated with the leukocytes themselves as well as with...

Novel Form of Adaptation in Mouse Retinal Rods Speeds Recovery of Phototransduction

Krispel, Claudia M., Chen, Ching-Kang, Simon, Melvin I., Burns, Marie E.

Photoreceptors of the retina adapt to ambient light in a manner that allows them to detect changes in illumination over an enormous range of intensities. We have discovered a novel form of adaptation...

Identification of an alternative Gαq-dependent chemokine receptor signal transduction pathway in dendritic cells and granulocytes

Shi, Guixiu, Partida-Sánchez, Santiago, Misra, Ravi S., Tighe, Michael, Borchers, Michael T., Lee, James J., ...

CD38 controls the chemotaxis of leukocytes to some, but not all, chemokines, suggesting that chemokine receptor signaling in leukocytes is more diverse than previously appreciated. To determine the...

Activation of G12/G13 Results in Shape Change and Rho/Rho-Kinase–mediated Myosin Light Chain Phosphorylation in Mouse Platelets

Klages, Birgit, Brandt, Ursula, Simon, Melvin I., Schultz, Günter, Offermanns, Stefan

Platelets respond to various stimuli with rapid changes in shape followed by aggregation and secretion of their granule contents. Platelets lacking the α-subunit of the heterotrimeric G protein Gq...

Molecular architecture of Gαo and the structural basis for RGS16-mediated deactivation

Slep, Kevin C., Kercher, Michele A., Wieland, Thomas, Chen, Ching-Kang, Simon, Melvin I., Sigler, Paul B.

Heterotrimeric G proteins relay extracellular cues from heptahelical transmembrane receptors to downstream effector molecules. Composed of an α subunit with intrinsic GTPase activity and a βγ...