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Stefan Offermanns - One of the best experts on this subject based on the ideXlab platform.
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Conditional mutaGenesis of G-protein coupled receptors and G-Proteins.
Handbook of experimental pharmacology, 2007Co-Authors: Stefan OffermannsAbstract:The G-protein-coupled receptor siGnalinG system, consistinG of a huGe variety of receptors as well as of many G-Proteins and effectors, operates in every cell and is involved in many physioloGical and patholoGical processes. The versatility of this system and the involvement of specific components makes G-protein-coupled receptors and their siGnalinG pathways ideal tarGets for pharmacoloGical interventions. Classical mouse knockout models have often provided important preliminary insiGhts into the bioloGical roles of individual receptors and siGnalinG pathways and they are routinely used in the process of tarGet validation. The recent development of efficient conditional mutaGenesis techniques now allows a much more detailed analysis of G-protein-mediated siGnalinG transduction processes. This review summarizes some of the areas in which proGress has recently been made by applyinG conditional mutaGenesis of Genes codinG for G-Proteins and G-protein-coupled receptors.
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mammalian G Proteins and their cell type specific functions
Physical Review, 2005Co-Authors: Nina Wettschureck, Stefan OffermannsAbstract:Heterotrimeric G Proteins are key players in transmembrane siGnalinG by couplinG a huGe variety of receptors to channel Proteins, enzymes, and other effector molecules. Multiple subforms of G Proteins toGether with receptors, effectors, and various reGulatory Proteins represent the components of a hiGhly versatile siGnal transduction system. G protein-mediated siGnalinG is employed by virtually all cells in the mammalian orGanism and is centrally involved in diverse physioloGical functions such as perception of sensory information, modulation of synaptic transmission, hormone release and actions, reGulation of cell contraction and miGration, or cell Growth and differentiation. In this review, some of the functions of heterotrimeric G Proteins in defined cells and tissues are described.
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G Proteins as transducers in transmembrane siGnallinG
Progress in Biophysics & Molecular Biology, 2003Co-Authors: Stefan OffermannsAbstract:The G-protein-mediated siGnallinG system has evolved as one of the most widely used transmembrane siGnallinG mechanisms in mammalian orGanisms. All mammalian cells express G-protein-coupled receptors as well as several types of heterotrimeric G-Proteins and effectors. G-protein-mediated siGnallinG is involved in many physioloGical and patholoGical processes. This review summarizes some General aspects of G-protein-mediated siGnallinG and focusses on recent data especially from studies in mutant mice which have elucidated some of the cellular and bioloGical functions of heterotrimeric G-prtoteins.
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Complex information processinG by the transmembrane siGnalinG system involvinG G Proteins
Naunyn-Schmiedeberg's Archives of Pharmacology, 1994Co-Authors: Stefan Offermanns, Günter SchultzAbstract:Much of the information cells receive is transduced by a membranous siGnalinG system that uses heterotrimeric Guanine nucleotide bindinG Proteins (G Proteins) to functionally couple cell surface receptors to a variety of effectors. DurinG recent years it has been shown that receptors, G protein α, β and γ subunits as well as effectors involved in this siGnalinG system exhibit a remarkable structural diversity and that the interactions of these components display a bewilderinG complexity. Even thouGh many questions remain to be answered, it is becominG obvious that G Proteins form the basis of a complex membranous siGnalinG network which allows the cell to coordinate and to process incominG siGnals already on the level of the plasma membrane.
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Identification of receptor-activated G Proteins: selective immunoprecipitation of photolabeled G-protein alpha subunits.
Methods in enzymology, 1994Co-Authors: Karl-ludwig Laugwitz, Günter Schultz, Karsten Spicher, Stefan OffermannsAbstract:Publisher Summary Reconstitution and cotransfection experiments are powerful tools to study the interaction of receptors, G Proteins, and effectors. To examine receptor–G-protein couplinG at natural concentrations of the individual components, methods for in situ determination of receptor–G-protein interaction have been developed. These approaches are based on the action of specific antisense oliGonucleotides or on the functional effects of subtype-specific antibodies. In some cases, G Proteins coupled to receptors can be identified with specific antibodies in isolated receptor–G-protein complexes or by receptor-stimulated adenosine diphosphate (ADP)-ribosylation of subunits by cholera toxin. This chapter describes the application of [ α - 32 P]Guanosine-5'-triphosphate (GTP) azidoanilide as a tool to label α subunits of receptor-activated G Proteins. Because the number of known G Proteins, which are defined by their α- subunits, has constantly increased, it was necessary to improve the selective identification of G-protein α subunits photolabeled in response to receptor activation. This was achieved by combininG photolabelinG of receptor-activated G Proteins by [ α - 32 P]GTP azidoanilide in membranes with immunoprecipitation of the photolabeled G-protein α subunits by subtype-specific antisera. Whereas this experimental approach is not suitable for identification of βγ complexes involved in receptor-G-protein couplinG, it allows the exact identification of receptor-activated G Proteins provided that specific precipitatinG antisera are available.
Henry R. Bourne - One of the best experts on this subject based on the ideXlab platform.
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how receptors talk to trimeric G Proteins
Current Opinion in Cell Biology, 1997Co-Authors: Henry R. BourneAbstract:Abstract Stimulated by hormones and sensory stimuli, serpentine receptors promote the release of GDP that is bound to the α subunit of trimeric G Proteins and its replacement by GTP. Recent investiGations have beGun to define the sizes, shapes, and relative orientations of receptors and G Proteins, the surfaces throuGh which they interact with one another, and conformational chanGes in both sets of molecules that underlie receptor-catalyzed Guanine-nucleotide exchanGe.
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lipid modifications of trimeric G Proteins
Journal of Biological Chemistry, 1995Co-Authors: Philip B Wedegaertner, Paul T Wilson, Henry R. BourneAbstract:G protein alpha subunits and beta Gamma dimers are covalently modified by lipids. The emerGinG picture is one in which attached lipids provide more than just a nonspecific "Glue" for stickinG G Proteins to membranes. We are only beGinninG to understand how different lipid modifications of different G protein subunits affect specific protein-protein interactions and localization to specific cellular sites. In addition, reGulation of these modifications, particularly palmitoylation, can provide new ways to reGulate siGnals transmitted by G Proteins.
Katsutoshi Goto - One of the best experts on this subject based on the ideXlab platform.
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orexin receptor type 1 couples exclusively to pertussis toxin insensitive G Proteins while orexin receptor type 2 couples to both pertussis toxin sensitive and insensitive G Proteins
Journal of Pharmacological Sciences, 2003Co-Authors: Yoshihiro Miwa, Megumi Shibahara, Toshihiko Yada, Takeshi Sakurai, Akihiro Yamanaka, Katsutoshi GotoAbstract:Abstract SiGnal transduction pathways of orexin receptors were examined usinG a nerve-like cell line transfected with orexin receptor type-1 (OX1R) and orexin receptor type-2 (OX2R). Forskolin-stimulated cyclic adenosine 3,5-monophosphate (cAMP) accumulation in OX2R-expressinG cells was inhibited by orexin in a dose-dependent manner, and the effect was abolished by pretreatment with pertussis toxin (PTX). The inhibitory effect of orexin on forskolin-stimulated cAMP accumulation was not observed in OX1R-expressinG cells. Administration of orexin to these cells resulted in a transient increase of intracellular calcium concentration ([Ca2+]i). Orexin-stimulated increases in [Ca2+]i in OX1R- or OX2R-expressinG cells were not affected by the PTX pretreatment. These observations suGGest that OX1R couples exclusively to PTX-insensitive G-Proteins, while OX2R couples to both PTX-sensitive and -insensitive G-Proteins. To examine the relative contributions of these G-Proteins in OX2R-mediated activation of neurons, we used histaminerGic tuberomammillary nucleus neurons, in which OX2R is abundantly expressed. We found that a phospholipase C (PLC)-inhibitor, U73122, inhibits orexin-mediated neuronal activation, but PTX showed no effect on it. This suGGests that althouGh OX2R couples to multiple G-Proteins, activation of neurons by orexins throuGh OX2R is mediated via a PTX-insensitive, PLC dependent pathway.
Yoshihiro Miwa - One of the best experts on this subject based on the ideXlab platform.
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orexin receptor type 1 couples exclusively to pertussis toxin insensitive G Proteins while orexin receptor type 2 couples to both pertussis toxin sensitive and insensitive G Proteins
Journal of Pharmacological Sciences, 2003Co-Authors: Yoshihiro Miwa, Megumi Shibahara, Toshihiko Yada, Takeshi Sakurai, Akihiro Yamanaka, Katsutoshi GotoAbstract:Abstract SiGnal transduction pathways of orexin receptors were examined usinG a nerve-like cell line transfected with orexin receptor type-1 (OX1R) and orexin receptor type-2 (OX2R). Forskolin-stimulated cyclic adenosine 3,5-monophosphate (cAMP) accumulation in OX2R-expressinG cells was inhibited by orexin in a dose-dependent manner, and the effect was abolished by pretreatment with pertussis toxin (PTX). The inhibitory effect of orexin on forskolin-stimulated cAMP accumulation was not observed in OX1R-expressinG cells. Administration of orexin to these cells resulted in a transient increase of intracellular calcium concentration ([Ca2+]i). Orexin-stimulated increases in [Ca2+]i in OX1R- or OX2R-expressinG cells were not affected by the PTX pretreatment. These observations suGGest that OX1R couples exclusively to PTX-insensitive G-Proteins, while OX2R couples to both PTX-sensitive and -insensitive G-Proteins. To examine the relative contributions of these G-Proteins in OX2R-mediated activation of neurons, we used histaminerGic tuberomammillary nucleus neurons, in which OX2R is abundantly expressed. We found that a phospholipase C (PLC)-inhibitor, U73122, inhibits orexin-mediated neuronal activation, but PTX showed no effect on it. This suGGests that althouGh OX2R couples to multiple G-Proteins, activation of neurons by orexins throuGh OX2R is mediated via a PTX-insensitive, PLC dependent pathway.
Daniel J. O'mahony - One of the best experts on this subject based on the ideXlab platform.
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Lipid modification of G Proteins.
Trends in cardiovascular medicine, 1994Co-Authors: B. Therese Kinsella, Daniel J. O'mahonyAbstract:The heterotrimeric Guanine nucleotide-bindinG G Proteins, composed of α, β, and γ subunits, act as siGnal transducers between cell surface receptors and downstream effector molecules, leadinG to chanGes in intracellular second messenGers. The superfamily of ras-related low-molecular-mass GTP-bindinG G Proteins is involved in a number of cellular functions, includinG cell differentiation and Growth control, actin polymerization and cytoskeleton arranGement, and intracellular vesicular transport. The heterotrimeric G Proteins and the ras-related low-molecular-mass G Proteins are modified in vivo by a number of lipid Groups, includinG palmitate, myristate, heteroGeneous fatty-acyl Groups (C12:0, C14:1, or C14:2 fatty-acyl Groups), and C15 farnesyl or C20 GeranylGeranyl isoprenoids. Lipid modification of G Proteins increases the hydrophobicity of the Proteins. In this review, we describe the various types of lipid modification of G Proteins and discuss the siGnificance of lipid modification with respect to G-protein function.
