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1.
A G protein-coupled receptor is a plasma membrane receptor for the plant hormone abscisic acid 总被引：4，自引：0，他引：4
The plant hormone abscisic acid (ABA) regulates many physiological and developmental processes in plants. The mechanism of ABA perception at the cell surface is not understood. Here, we report that a G protein-coupled receptor genetically and physically interacts with the G protein alpha subunit GPA1 to mediate all known ABA responses in Arabidopsis. Overexpressing this receptor results in an ABA-hypersensitive phenotype. This receptor binds ABA with high affinity at physiological concentration with expected kinetics and stereospecificity. The binding of ABA to the receptor leads to the dissociation of the receptor-GPA1 complex in yeast. Our results demonstrate that this G protein-coupled receptor is a plasma membrane ABA receptor. 相似文献
2.
Cells migrating directionally toward a chemoattractant source display a highly polarized cytoskeletal organization, with F-actin localized predominantly at the anterior and myosin II at the lateral and posterior regions. Dictyostelium discoideum has proven a useful system for elucidating signaling pathways that regulate this chemotactic response. During development, extracellular adenosine 3', 5' monophosphate (cAMP) functions as a primary signal to activate cell surface cAMP receptors (cARs). These receptors transduce different signals depending on whether or not they are coupled to heterotrimeric guanine nucleotide-binding proteins (G proteins) (see the STKE Connections Maps). Multiple G protein-stimulated pathways interact to establish polarity in chemotaxing D. discoideum cells by localizing F-actin at their leading edge and by regulating the phosphorylation state and assembly of myosin II. Many of the molecular interactions described are fundamental to the regulation of chemotaxis in other eukaryotic cells. 相似文献
3.
Golf: an olfactory neuron specific-G protein involved in odorant signal transduction 总被引：34，自引：0，他引：34
Biochemical and electrophysiological studies suggest that odorants induce responses in olfactory sensory neurons via an adenylate cyclase cascade mediated by a G protein. An olfactory-specific guanosine triphosphate (GTP)-binding protein alpha subunit has now been characterized and evidence is presented suggesting that this G protein, termed Golf, mediates olfaction. Messenger RNA that encodes Golf alpha is expressed in olfactory neuroephithelium but not in six other tissues tested. Moreover, within the olfactory epithelium, Golf alpha appears to be expressed only by the sensory neurons. Specific antisera were used to localize Golf alpha protein to the sensory apparatus of the receptor neurons. Golf alpha shares extensive amino acid identity (88 percent) with the stimulatory G protein, Gs alpha. The expression of Golf alpha in S49 cyc- kin- cells, a line deficient in endogenous stimulatory G proteins, demonstrates its capacity to stimulate adenylate cyclase in a heterologous system. 相似文献
4.
P S Klein T J Sun C L Saxe A R Kimmel R L Johnson P N Devreotes 《Science (New York, N.Y.)》1988,241(4872):1467-1472
During the early stages of its developmental program, Dictyostelium discoideum expresses cell surface cyclic adenosine monophosphate (cyclic AMP) receptors. It has been suggested that these receptors coordinate the aggregation of individual cells into a multicellular organism and regulate the expression of a large number of developmentally regulated genes. The complementary DNA (cDNA) for the cyclic AMP receptor has now been cloned from lambda gt-11 libraries by screening with specific antiserum. The 2-kilobase messenger RNA (mRNA) that encodes the receptor is undetectable in growing cells, rises to a maximum at 3 to 4 hours of development, and then declines. In vitro transcribed complementary RNA, when hybridized to cellular mRNA, specifically arrests in vitro translation of the receptor polypeptide. When the cDNA is expressed in Dictyostelium cells, the undifferentiated cells specifically bind cyclic AMP. Cell lines transformed with a vector that expresses complementary mRNA (antisense) do not express the cyclic AMP receptor protein. These cells fail to enter the aggregation stage of development during starvation, whereas control and wild-type cells aggregate and complete the developmental program within 24 hours. The phenotype of the antisense transformants suggests that the cyclic AMP receptor is essential for development. The deduced amino acid sequence of the receptor reveals a high percentage of hydrophobic residues grouped in seven domains, similar to the rhodopsins and other receptors believed to interact with G proteins. It shares amino acid sequence identity and is immunologically cross-reactive with bovine rhodopsin. A model is proposed in which the cyclic AMP receptor crosses the bilayer seven times with a serine-rich cytoplasmic carboxyl terminus, the proposed site of ligand-induced receptor phosphorylation. 相似文献
5.
From epinephrine to cyclic AMP 总被引：17，自引：0，他引：17
A Levitzki 《Science (New York, N.Y.)》1988,241(4867):800-806
Binding of catecholamines to the beta-adrenergic receptor results in the activation of adenylate cyclase and the intracellular formation of adenosine 3',5'-monophosphate (cAMP). In the past 20 years the events that lead from hormone binding at the cell surface receptor site to the synthesis of cAMP at the inner layer of the membrane have been intensively studied. Signal transduction in this system involves the sequential interaction of the beta-adrenergic receptor with the guanine nucleotide-binding protein (Gs) and the adenylate cyclase catalyst (C). The mechanism of signal transduction from the receptor through Gs to C, as well as the role of the adenylate cyclase inhibitory G protein Gi, is discussed. 相似文献
6.
Wang Q Zhao J Brady AE Feng J Allen PB Lefkowitz RJ Greengard P Limbird LE 《Science (New York, N.Y.)》2004,304(5679):1940-1944
Arrestin regulates almost all G protein-coupled receptor (GPCR)-mediated signaling and trafficking. We report that the multidomain protein, spinophilin, antagonizes these multiple arrestin functions. Through blocking G protein receptor kinase 2 (GRK2) association with receptor-Gbetagamma complexes, spinophilin reduces arrestin-stabilized receptor phosphorylation, receptor endocytosis, and the acceleration of mitogen-activated protein kinase (MAPK) activity following endocytosis. Spinophilin knockout mice were more sensitive than wild-type mice to sedation elicited by stimulation of alpha2 adrenergic receptors, whereas arrestin 3 knockout mice were more resistant, indicating that the signal-promoting, rather than the signal-terminating, roles of arrestin are more important for certain response pathways. The reciprocal interactions of GPCRs with spinophilin and arrestin represent a regulatory mechanism for fine-tuning complex receptor-orchestrated cell signaling and responses. 相似文献
7.
A G protein mutant that inhibits thrombin and purinergic receptor activation of phospholipase A2 总被引：7，自引：0，他引：7
The stimulation of phospholipase A2 by thrombin and type 2 (P2)-purinergic receptor agonists in Chinese hamster ovary cells is mediated by the G protein Gi. To delineate alpha chain regulatory regions responsible for control of phospholipase A2, chimeric cDNAs were constructed in which different lengths of the alpha subunit of Gs (alpha s) were replaced with the corresponding sequence of the Gi alpha subunit (alpha i2). When a carboxyl-terminal chimera alpha s-i(38), which has the last 38 amino acids of alpha s substituted with the last 36 residues of alpha i2, was expressed in Chinese hamster ovary cells, the receptor-stimulated phospholipase A2 activity was inhibited, although the chimera could still activate adenylyl cyclase. Thus, alpha s-i(38) is an active alpha s, but also a dominant negative alpha i molecule, indicating that the last 36 amino acids of alpha i2 are a critical domain for G protein regulation of phospholipase A2 activity. 相似文献
8.
Periodic signaling controlled by an oscillatory circuit that includes protein kinases ERK2 and PKA 总被引：1，自引：0，他引：1
Maeda M Lu S Shaulsky G Miyazaki Y Kuwayama H Tanaka Y Kuspa A Loomis WF 《Science (New York, N.Y.)》2004,304(5672):875-878
Self-regulating systems often use robust oscillatory circuits. One such system controls the chemotactic signaling mechanism of Dictyostelium, where pulses of adenosine 3',5'-monophosphate (cAMP) are generated with a periodicity of 7 minutes. We have observed spontaneous oscillations in activation of the mitogen-activated protein (MAP) kinase ERK2 that occur in phase with peaks of cAMP, and we show that ERK2 modulates cAMP levels through the phosphodiesterase RegA. Computer modeling and simulations of the underlying circuit faithfully account for the ability of the cells to spontaneously generate periodic pulses during specific stages of development. Similar oscillatory processes may occur in cells of many different species. 相似文献
9.
Sequence-specific binding of human Ets-1 to the T cell receptor alpha gene enhancer 总被引：48，自引：0，他引：48
I C Ho N K Bhat L R Gottschalk T Lindsten C B Thompson T S Papas J M Leiden 《Science (New York, N.Y.)》1990,250(4982):814-818
10.
Direct activation of mammalian atrial muscarinic potassium channels by GTP regulatory protein Gk 总被引：41，自引：0，他引：41
The mammalian heart rate is regulated by the vagus nerve, which acts via muscarinic acetylcholine receptors to cause hyperpolarization of atrial pacemaker cells. The hyperpolarization is produced by the opening of potassium channels and involves an intermediary guanosine triphosphate-binding regulatory (G) protein. Potassium channels in isolated, inside-out patches of membranes from atrial cells now are shown to be activated by a purified pertussis toxin-sensitive G protein of subunit composition alpha beta gamma, with an alpha subunit of 40,000 daltons. Thus, mammalian atrial muscarinic potassium channels are activated directly by a G protein, not indirectly through a cascade of intermediary events. The G protein regulating these channels is identified as a potent Gk; it is active at 0.2 to 1 pM. Thus, proteins other than enzymes can be under control of receptor coupling G proteins. 相似文献
11.
A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins 总被引：89，自引：0，他引：89
C A Smith T Davis D Anderson L Solam M P Beckmann R Jerzy S K Dower D Cosman R G Goodwin 《Science (New York, N.Y.)》1990,248(4958):1019-1023
12.
Control of yeast mating signal transduction by a mammalian beta 2-adrenergic receptor and Gs alpha subunit 总被引：6，自引：0，他引：6
K King H G Dohlman J Thorner M G Caron R J Lefkowitz 《Science (New York, N.Y.)》1990,250(4977):121-123
To facilitate functional and mechanistic studies of receptor-G protein interactions, [corrected] the human beta 2-adrenergic receptor (h beta-AR) has been expressed in Saccharomyces cerevisiae. This was achieved by placing a modified h beta-AR gene under control of the galactose-inducible GAL1 promoter. After induction by galactose, functional h beta-AR was expressed at a concentration several hundred times as great as that found in any human tissue. As determined from competitive ligand binding experiments, h beta-AR expressed in yeast displayed characteristic affinities, specificity, and stereoselectivity. Partial activation of the yeast pheromone response pathway by beta-adrenergic receptor agonists was achieved in cells coexpressing h beta-AR and a mammalian G protein (Gs) alpha subunit-demonstrating that these components can couple to each other and to downstream effectors when expressed in yeast. This in vivo reconstitution system provides a new approach for examining ligand binding and G protein coupling to cell surface receptors. 相似文献
13.
R Guy S J Ullrich M Foo-Philips K S Hathcock E Appella R J Hodes 《Science (New York, N.Y.)》1989,244(4911):1477-1480
Although the T cell receptor (TCR) alpha beta heterodimer and its encoding genes have been characterized, a cell-free form of this receptor, which is needed for the study of functional or ligand-binding properties of the receptor, has not previously been isolated. When the cell-free supernatant products of activated cloned T helper (TH) cells were found to mediate helper activity with antigen specificity identical to that of intact T cells, experiments were carried out to determine whether this functional activity was mediated by a cell-free form of TCR-related material. A disulfide-linked dimer indistinguishable from the T cell surface alpha beta heterodimer was precipitated from cell-free supernatants of cloned TH cells with F23.1, a monoclonal antibody specific for a TCR V beta 8 determinant. Moreover, when cell-free TH products were bound to and eluted from immobilized F23.1, these affinity-purified materials had antigen-specific and major histocompatibility complex-restricted helper activity that synergized with recombinant lymphokines in the generation of B cell antibody responses. These findings suggest that the factor isolated from T cell supernatants is a cell-free form of the TCR alpha beta dimer. 相似文献
14.
Glycolipid antigen processing for presentation by CD1d molecules 总被引：3，自引：0，他引：3
Prigozy TI Naidenko O Qasba P Elewaut D Brossay L Khurana A Natori T Koezuka Y Kulkarni A Kronenberg M 《Science (New York, N.Y.)》2001,291(5504):664-667
The requirement for processing glycolipid antigens in T cell recognition was examined with mouse CD1d-mediated responses to glycosphingolipids (GSLs). Although some disaccharide GSL antigens can be recognized without processing, the responses to three other antigens, including the disaccharide GSL Gal(alpha1-->2)GalCer (Gal, galactose; GalCer, galactosylceramide), required removal of the terminal sugars to permit interaction with the T cell receptor. A lysosomal enzyme, alpha-galactosidase A, was responsible for the processing of Gal(alpha1-->2)GalCer to generate the antigenic monosaccharide epitope. These data demonstrate a carbohydrate antigen processing system analogous to that used for peptides and an ability of T cells to recognize processed fragments of complex glycolipids. 相似文献
15.
Although the biological actions of the cell membrane and serum lipid lysophosphatidylcholine (LPC) in atherosclerosis and systemic autoimmune disease are well recognized, LPC has not been linked to a specific cell-surface receptor. We show that LPC is a high-affinity ligand for G2A, a lymphocyte-expressed G protein-coupled receptor whose genetic ablation results in the development of autoimmunity. Activation of G2A by LPC increased intracellular calcium concentration, induced receptor internalization, activated ERK mitogen-activated protein kinase, and modified migratory responses of Jurkat T lymphocytes. This finding implicates a role for LPC-G2A interaction in the etiology of inflammatory autoimmune disease and atherosclerosis. 相似文献
16.
Diversity of G proteins in signal transduction 总被引：123，自引：0，他引：123
The heterotrimeric guanine nucleotide-binding proteins (G proteins) act as switches that regulate information processing circuits connecting cell surface receptors to a variety of effectors. The G proteins are present in all eukaryotic cells, and they control metabolic, humoral, neural, and developmental functions. More than a hundred different kinds of receptors and many different effectors have been described. The G proteins that coordinate receptor-effector activity are derived from a large gene family. At present, the family is known to contain at least sixteen different genes that encode the alpha subunit of the heterotrimer, four that encode beta subunits, and multiple genes encoding gamma subunits. Specific transient interactions between these components generate the pathways that modulate cellular responses to complex chemical signals. 相似文献
17.
18.
Observations made with the x-ray satellite ROSAT (Roentgen Satellite) have produced the first spatially resolved x-ray image of a corona around a star like our sun. The star is the secondary in the eclipsing binary system alpha Coronae Borealis (CrB), which consists of one star of spectral type A0V and one of type G5V. The x-ray light curve of alpha CrB shows a total x-ray eclipse during secondary optical minimum, with the G star behind the A star. The totality of the eclipse demonstrates that the A-type component in alpha CrB is x-ray dark and that the x-ray flux arises exclusively from the later-type companion. The x-ray eclipse ingress and egress are highly asymmetric compared with the optical eclipse, indicating a highly asymmetric x-ray intensity distribution on the surface of the G star. From a detailed modeling of the ingress and egress of the x-ray light curve, an eclipse map of the G star was constructed by a method based on an optimization by simulated annealing. 相似文献
19.
Chen JG Willard FS Huang J Liang J Chasse SA Jones AM Siderovski DP 《Science (New York, N.Y.)》2003,301(5640):1728-1731
G protein-coupled receptors (GPCRs) at the cell surface activate heterotrimeric G proteins by inducing the G protein alpha (Galpha) subunit to exchange guanosine diphosphate for guanosine triphosphate. Regulators of G protein signaling (RGS) proteins accelerate the deactivation of Galpha subunits to reduce GPCR signaling. Here we identified an RGS protein (AtRGS1) in Arabidopsis that has a predicted structure similar to a GPCR as well as an RGS box with GTPase accelerating activity. Expression of AtRGS1 complemented the pheromone supersensitivity phenotype of a yeast RGS mutant, sst2Delta. Loss of AtRGS1 increased the activity of the Arabidopsis Galpha subunit, resulting in increased cell elongation in hypocotyls in darkness and increased cell production in roots grown in light. These findings suggest that AtRGS1 is a critical modulator of plant cell proliferation. 相似文献
20.
cDNA expression cloning of the IL-1 receptor, a member of the immunoglobulin superfamily 总被引：65，自引：0，他引：65
J E Sims C J March D Cosman M B Widmer H R MacDonald C J McMahan C E Grubin J M Wignall J L Jackson S M Call 《Science (New York, N.Y.)》1988,241(4865):585-589
Interleukin-1 alpha and -1 beta (IL-1 alpha and IL-1 beta) are cytokines that participate in the regulation of immune responses, inflammatory reactions, and hematopoiesis. A direct expression strategy was used to clone the receptor for IL-1 from mouse T cells. The product of the cloned complementary DNA binds both IL-1 alpha and IL-1 beta in a manner indistinguishable from that of the native T cell IL-1 receptor. The extracellular, IL-1 binding portion of the receptor is 319 amino acids in length and is composed of three immunoglobulin-like domains. The cytoplasmic portion of the receptor is 217 amino acids long. 相似文献