Keywords: G Protein-coupled Receptors (12)

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BOTANY: A Plant Receptor with a Big Family
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BOTANY: A Plant Receptor with a Big Family

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Access to the article is free, however registration and sign-in are required. A hormone that controls plant development and survival acts through a member of a receptor family whose other members are pervasive in animal cells. (less)

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Author:
Alexander Christmann (Technical University Munich;Department of Plant Science)
Erwin Grill (Technical University Munich;Department of Plant Science)
CELL SIGNALING: Beta-Arrestin, a Two-fisted Terminator
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CELL SIGNALING: Beta-Arrestin, a Two-fisted Terminator

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Access to the article is free, however registration and sign-in are required. Beta-arrestin escorts enzymes to activated receptors, catalyzing the demise of signals that are generated. This may be a common theme among G protein-coupled receptors. (less)

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Eileen F. Grady (University of California, San Francisco;UCSF Center for the Neurobiology of Digestive Disease)
G-Protein Coupled Receptors: Vision and Disease, Spring 2007
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G-Protein Coupled Receptors: Vision and Disease, Spring 2007

How do we communicate with the outside world? How are our senses ... (more)

How do we communicate with the outside world? How are our senses of vision, smell, taste and pain controlled at the cellular and molecular levels? What causes medical conditions like allergies, hypertension, depression, obesity and various central nervous system disorders? G-protein coupled receptors (GPCRs) provide a major part of the answer to all of these questions. GPCRs constitute the largest family of cell-surface receptors and in humans are encoded by more than 1,000 genes. GPCRs convert extracellular messages into intracellular responses and are involved in essentially all physiological processes. GPCR dysfunction results in numerous human disorders, and over 50% of all prescription drugs on the market today directly or indirectly target GPCRs.In this course, we will discuss GPCR signal transduction pathways, GPCR oligomerization and the diseases caused by GPCR dysfunction. We will study the structure and function of rhodopsin, a dim-light photoreceptor and a well-studied GPCR that converts light into electric impulses sent to the brain and leads to vision. We will also discuss how mutations in rhodopsin cause retinal degeneration and congenital night blindness. This course is one of many Advanced Undergraduate Seminars offered by the Biology Department at MIT. These seminars are tailored for students with an interest in using primary research literature to discuss and learn about current biological research in a highly interactive setting. Many instructors of the Advanced Undergraduate Seminars are postdoctoral scientists with a strong interest in teaching. (less)

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Kota, Parvathi
G{alpha}q and Phospholipase C-{beta}: Turn On, Turn Off, and Do It Fast
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G{alpha}q and Phospholipase C-{beta}: Turn On, Turn Off, and Do It Fast

Heterotrimeric G proteins and G protein–coupled receptors represent conserved protein families with ... (more)

Heterotrimeric G proteins and G protein–coupled receptors represent conserved protein families with origins in the prokaryotes, but the various G protein–regulated effectors are heterogeneous in structure and function. The effectors apparently evolved ways to listen to G proteins late in their evolutionary histories. The structure of a complex between the effector protein phospholipase C-β3 (PLC-β3) and its activator, Gαq, suggests that several effectors independently evolved a structurally similar helix-turn-helix segment for G protein recognition. PLC-βs are also guanosine triphosphatase (GTPase)–activating proteins (GAPs) for the Gq that activates them. In a second example of convergent evolution, the GAP activity of these proteins depends on a flexible asparagine-containing loop that resembles the GAP site on RGS proteins, another family of G protein GAPs. Together, these two sites are proposed to cooperate to enable fast binding to activated Gαq, followed by fast deactivation. This cycle allows rapid sampling of the activation state of Gq-coupled receptors while providing efficient signal transduction. (less)

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Author:
Elliott M. Ross (University of Texas Southwestern Medical Center;Department of Pharmacology REV)
An Insider's View
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An Insider's View

This article introduces a special section on the study of cell signaling ... (more)

This article introduces a special section on the study of cell signaling and regulatory pathways. This special issue includes an eclectic selection of topics chosen to reflect the nature of current signaling research and the viewpoints of authorities who have recently contributed detailed descriptions of cell regulatory pathways to the Database of Cell Signaling at Science's STKE (see www.sciencemag.org/sciext/cellsignaling07/). These pathways describe mechanisms that underlie leading causes of life-threatening diseases (such as heart disease and cancer), control excessive stimulation of the immune system (like that in patients suffering from arthritis), and regulate development and a range of environmental responses in plants. (less)

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Elizabeth Adler (AAAS;)
John Foley (AAAS;)
L. Bryan Ray (AAAS;)
Nancy Gough (AAAS;)
Matching Accessories
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Matching Accessories

Heterodimerization enhances the complexity of ligand recognition and diversity of signaling responses ... (more)

Heterodimerization enhances the complexity of ligand recognition and diversity of signaling responses of heterotrimeric guanine nucleotide-binding protein-coupled receptors (GPCRs). Many accessory proteins (for ion channels or GPCRs) appear to associate with their partners relatively early in the process whereby proteins are transported to the cell surface; their roles in modulating function may have evolved out of simple proximity to a protein that once upon a time they either facilitated or accompanied through the maturation process. The receptor activity-modifying proteins (RAMPs) are a family of single-transmembrane accessory proteins that heterodimerize with GPCRs and, thereby, allow individual GPCRs to recognize multiple ligands and to activate various signaling pathways in response to ligand binding. The M10 family of major histocompatibility complex (MHC) class 1b proteins has recently been shown to associate with murine vomeronasal V2R receptors, as well as to escort them to the cell surface. The exact role of M10 in modulating V2R function (or vice versa) remains to be determined. (less)

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Author:
Steven M. Foord (Stevenage;Target Bioinformatics, GlaxoSmithKline Medicine Research Centre REV)
Molecular Scaffolds Regulate Bidirectional Crosstalk Between Wnt and Classical Seven-Transmembrane Domain Receptor Signaling Pathways
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Molecular Scaffolds Regulate Bidirectional Crosstalk Between Wnt and Classical Seven-Transmembrane Domain Receptor Signaling Pathways

Signaling downstream of classical seven-transmembrane domain receptors (7TMRs) had generally been thought ... (more)

Signaling downstream of classical seven-transmembrane domain receptors (7TMRs) had generally been thought to recruit factors that are in large part separate from those recruited by atypical 7TMRs, such as Frizzleds (Fzs), receptors for the Wnt family of glycoproteins. Classical 7TMRs are also known as G protein–coupled receptors (GPCRs) and are mediated by signaling factors such as heterotrimeric guanine nucleotide–binding proteins (G proteins), GPCR kinases (GRKs), and β-arrestins. Over the past few years, it has become increasingly apparent that classical and atypical 7TMRs share these factors, which are often associated with mediating classical 7TMR signaling, as well as the scaffolding proteins that were initially thought to be involved in transmitting atypical 7TMR signals. This sharing of signaling components by agonists that bind classical 7TMRs and those binding to atypical 7TMRs establishes the possibility of extensive crosstalk between these receptor classes. We discuss the evidence for, and against, crosstalk, and examine mechanisms by which this can occur. (less)

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Author:
Kathleen Woulfe (Thomas Jefferson University;The Center for Translational Medicine REV)
Risto Kerkela (Thomas Jefferson University;The Center for Translational Medicine REV)
Thomas Force (Thomas Jefferson University;The Center for Translational Medicine REV)
Walter J. Koch (Thomas Jefferson University;The Center for Translational Medicine REV)
Rapid Actions of Steroid Receptors in Cellular Signaling Pathways
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Rapid Actions of Steroid Receptors in Cellular Signaling Pathways

Steroid hormones control diverse processes in reproduction and development. In target cells, ... (more)

Steroid hormones control diverse processes in reproduction and development. In target cells, they diffuse through the plasma membrane and bind to cytoplasmic receptors that mediate their action. Upon hormone binding, the steroid receptors undergo a conformational change and translocate to the nucleus, where they bind discrete nucleotide sequences to enhance the expression of specific genes. Steroid receptors also negatively regulate gene expression by binding to and down-regulating the activity of distinct transcription factors involved in cell proliferation, differentiation, and programmed cell death. Because all these responses require nuclear localization of the receptors, they are termed genomic functions, and they require about 30 to 60 minutes. These regulatory properties of steroid hormones can be distinguished from more rapid actions (<10 minutes) reminiscent of the activities of peptide hormones in the activation of signal transduction cascades. The mechanisms involved in initiating the rapid responses are still unclear, but they range from contributions of unidentified receptors to the involvement of heterotrimeric guanosine triphosphate-binding proteins (G proteins), or even the classical steroid receptors. Considerable advances have been made recently in the elucidation of the rapid responses mediated by steroid receptors. Accumulating evidence shows that a small but significant percentage of the conventional steroid receptors reside at the plasma membrane after ligand binding. From this location, they trigger diverse signaling cascades needed for cell proliferation and other biological processes. The effector molecules activated by the steroid receptors include mitogen-activated protein kinases (MAPKs), adenylyl cyclase (AC), phosphatidylinositol 3-kinase (PI3K), and protein kinase C (PKC). Thus, steroid receptors integrate classical functions as transcription factors in the nucleus with functions as signaling molecules at the plasma membrane. These two properties together make up the entire repertoire of regulatory functions so far attributed to steroid hormones. (less)

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Author:
Andrea Nestl (Institute of Toxicology and Genetics;Forschungszentrum Karlsruhe REV)
Andrew C. B. Cato (Institute of Toxicology and Genetics;Forschungszentrum Karlsruhe REV)
Sigrun Mink (Institute of Toxicology and Genetics;Forschungszentrum Karlsruhe REV)
Regulation of Cardiac Excitation-Contraction Coupling: A Cellular Update
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Regulation of Cardiac Excitation-Contraction Coupling: A Cellular Update

The primary purpose of this paper is to present a basic overview ... (more)

The primary purpose of this paper is to present a basic overview of some "relatively" new ideas related to the regulation of cardiac performance and underlying excitation-contraction (EC) coupling that have yet to be incorporated to textbooks currently used for introductory graduate-level physiology courses. Within the context of cardiac EC coupling, this review incorporates information on microdomains and local control theory, with particular emphasis on the role of Ca2+ sparks as a key regulatory component of ventricular myocyte contraction dynamics. Recent information pertaining to Ca2+ release mechanisms specific to the sarcoplasmic reticulum is also presented, as well as the idea of the ryanodine receptor as a macromolecular signaling complex. Because of the potential relationship to maladaptive functional responses under conditions of cardiovascular pathology, the regulatory role of cardiac adrenergic and additional G protein-coupled receptors known to regulate cardiac function is included, and fundamental concepts related to intracellular signaling are discussed. Finally, information on the roles of vascular and cardiac nitric oxide as an important regulator of cardiac performance is included to allow students to begin to think about the ubiquitous role of nitric oxide in the regulation of the cardiovascular system. An important point of emphasis is that whole organ cardiac dynamics can be traced back to the cellular events regulating intracellular Ca2+ homeostasis and as such provides an important conceptual framework from which the students can begin to think about whole organ physiology in health and disease. (less)

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PhD Donna H. Korzick (Pennsylvania State University Dept. of Physiology and Kinesiology)
Seven-Transmembrane Receptor Signaling Through {beta}-Arrestin
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Seven-Transmembrane Receptor Signaling Through {beta}-Arrestin

Cell surface receptors are important communicators of external stimuli to the cell ... (more)

Cell surface receptors are important communicators of external stimuli to the cell interior where they lead to initiation of various signaling pathways and cellular responses. The largest receptor family is the seven-transmembrane receptor (7TMR) family, with approximately 1000 coding genes in the human genome. When 7TMRs are stimulated with agonists, they activate heterotrimeric guanine nucleotide-binding proteins (G proteins), leading to the production of signaling second messengers, such as adenosine 3&prime;,5&prime;-monophosphate, inositol phosphates, and others. Activated receptors are rapidly phosphorylated on serine and threonine residues by specialized enzymes called G protein&ndash;coupled receptor kinases. Phosphorylated receptors bind the multifunctional adaptor proteins &beta;-arrestin1 and &beta;-arrestin2 with high affinity. &beta;-arrestin binding blocks further G protein coupling, leading to "desensitization" of G protein&ndash;dependent signaling pathways. For several years, this was considered the sole function of &beta;-arrestins. However, novel functions of &beta;-arrestins have been discovered. &beta;-arrestins are now designated as important adaptors that link receptors to the clathrin-dependent pathway of internalization. &beta;-arrestins bind and direct the activity of several nonreceptor tyrosine kinases in response to 7TMR stimulation. &beta;-arrestins also bind and scaffold members of such signaling cascades as the mitogen-activated protein kinases (MAPKs). &beta;-arrestins are crucial components in 7TMR signaling leading to cellular responses that include cell survival and chemotaxis. &beta;-arrestins act as endocytic adaptors and signal mediators not only for the 7TMRs, but also for several receptor tyrosine kinases. (less)

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Robert J. Lefkowitz (Duke University Medical Center;Department of Medicine REV)
Sudha K. Shenoy (Howard Hughes Medical Institute;Department of Medicine REV)
Size, Mates, and Fates
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Size, Mates, and Fates

This perspective introduces a special section on pathways initiated by three different ... (more)

This perspective introduces a special section on pathways initiated by three different types of receptors: brassinosteroid receptors that control plant size, G protein-coupled receptors that control mating responses in yeast, and Notch receptors that control cell fate in animals. (less)

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Elizabeth Adler (AAAS;)
L. Bryan Ray (AAAS;)
Nancy Gough (AAAS;)
TRKing Signals Through the Golgi
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TRKing Signals Through the Golgi

The subcellular localization of transmembrane receptors and other signaling proteins has emerged ... (more)

The subcellular localization of transmembrane receptors and other signaling proteins has emerged as a key component in the regulation of the intensity and specificity of their activity. Recent research indicates that immature TrkA neurotrophin receptors are transactivated in the Golgi apparatus after stimulation of neuropeptide pituitary adenylate cyclase&ndash;activating polypeptide PAC1 receptors or adenosine A2A receptors. Transactivation occurs independently of the TrkA extracellular ligand, nerve growth factor (NGF), through a signaling pathway that is distinct from that used in the transactivation of other receptor tyrosine kinases and has consequences distinct from those elicited by NGF at the plasma membrane. (less)

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Alexander Sorkin (University of Colorado Health Sciences Center;Department of Pharmacology REV)
2002 llaF ,gnivloS melborP gnireenignE dna sretupmoC ot noitcudortnI

2002 llaF ,gnivloS melborP gnireenignE dna sretupmoC ot noitcudortnI

.desu si egaugnal gnimmargorp avaJ ehT .gninnalp dna ,tnemeganam ,ecneics ,gnireenigne ni ... (more)

.desu si egaugnal gnimmargorp avaJ ehT .gninnalp dna ,tnemeganam ,ecneics ,gnireenigne ni smelborp gnivlos rof seuqinhcet gnipoleved no si sisahpmE .scipot decnavda detceles dna scihparg retupmoc ,gnihcraes dna gnitros ,serutcurts atad ,sdohtem laciremun ,secafretni resu lacihparg ,stpecnoc gnimmargorp revoc smelborp gnimmargorp ylkeeW .esruoc eht fo sucof eht si tnempoleved dna ngised erawtfos detneiro-tcejbO .snoitacilppa cifitneics dna gnireenigne rof sdohtem lanoitatupmoc dna tnempoleved erawtfos latnemadnuf stneserp esruoc sihT (less)