Allosteric and transmembrane signaling are among the major questions of structural biology. Here, we review and discuss signal transduction in four-helical TM bundles, focusing on histidine kinases and chemoreceptors found in two-component systems. Previously, piston, scissors, and helical rotation have been proposed as the mechanisms of TM signaling. We discuss theoretically possible conformational changes and examine the available experimental data, including the recent crystallographic structures of nitrate/nitrite sensor histidine kinase NarQ and phototaxis system NpSRII:NpHtrII. We show that (...) TM helices can flex at multiple points and argue that the various conformational changes are not mutually exclusive, and often are observed concomitantly, throughout the TM domain or in its part. The piston and scissoring motions are the most prominent motions in the structures, but more research is needed for definitive conclusions. Models of allosteric transmembrane signaling in microbial sensor histidine kinases and chemoreceptors are discussed in light of recent crystallographic structures. It is shown that the TM α-helices are flexible and various conformational changes are often observed concomitantly. The piston and scissoring motions are the most prominent in the structures. (shrink)

It has long been thought that transmembrane cell‐surface receptors, such as receptor tyrosine kinases and cytokine receptors, among others, are activated by ligand binding through ligand‐induced dimerization of the receptors. However, there is growing evidence that prior to ligand binding, various transmembrane receptors have a preformed, yet inactive, dimeric structure on the cell surface. Various studies also demonstrate that during transmembrane signaling, ligand binding to the extracellular domain of receptor dimers induces a rotation of transmembrane (...) domains, followed by rearrangement and/or activation of intracellular domains. The paper here describes transmembrane cell‐surface receptors that are known or proposed to exist in dimeric form prior to ligand binding, and discusses how these preformed dimers are activated by ligand binding. (shrink)

Steroid hormones are signaling molecules important for normal growth, development and differentiation of multicellular organisms. Brassinosteroids (BRs) are a class of polyhydroxylated steroids that are necessary for plant development. Molecular genetic studies in Arabidopsis thaliana have led to the cloning and characterization of the BR receptor, BRI1, which is a transmembrane receptor serine/threonine kinase. The extracellular domain of BRI1, which is composed mainly of leucine‐rich repeats, can confer BR responsivity to heterologous cells and is required for BR binding. (...) Although downstream components of BR action are mostly unknown, multiple genes whose expression are regulated by BRs have been identified and suggest mechanisms by which BRs affect cell elongation and division. BioEssays 23:1028–1036, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Motile bacteria respond to environmental cues to move to more favorable locations. The components of the chemotaxis signal transduction systems that mediate these responses are highly conserved among prokaryotes including both eubacterial and archael species. The best‐studied system is that found in Escherichia coli. Attractant and repellant chemicals are sensed through their interactions with transmembrane chemoreceptor proteins that are localized in multimeric assemblies at one or both cell poles together with a histidine protein kinase, CheA, an SH3‐like adaptor protein, (...) CheW, and a phosphoprotein phosphatase, CheZ. These multimeric protein assemblies act to control the level of phosphorylation of a response regulator, CheY, which dictates flagellar motion. Bacterial chemotaxis is one of the most‐understood signal transduction systems, and many biochemical and structural details of this system have been elucidated. This is an exciting field of study because the depth of knowledge now allows the detailed molecular mechanisms of transmembrane signaling and signal processing to be investigated. BioEssays 28:9–22, 2006. © 2005 Wiley Periodicals, Inc. (shrink)

G protein‐coupled receptors (GPCRs) are the largest family of transmembrane receptors and primarily signal through two main effector proteins: G proteins and β‐arrestins. Many agonists of GPCRs promote “biased” responses, in which different cellular signaling pathways are activated with varying efficacies. The mechanisms underlying biased signaling have not been fully elucidated, with many potential “hidden variables” that regulate this behavior. One contributor is “location bias,” which refers to the generation of unique signaling cascades from a given (...) GPCR depending upon the cellular location at which the receptor is signaling. Here, we review evidence that GPCRs are expressed at and traffic to various subcellular locations and discuss how location bias can impact the pharmacologic properties and characterization of GPCR agonists. We also evaluate how differences in subcellular environments can modulate GPCR signaling, highlight the physiological significance of subcellular GPCR signaling, and discuss the therapeutic potential of exploiting GPCR location bias. (shrink)

Cell shape and cell contacts are determined by transmembrane receptor‐mediated associations of the cytoskeleton with specific extracellular matrix proteins and with ligands on the surface of adjacent cells. The cytoplasmic domains of these microfilament‐membrane associations at the adherens junction sites, also Iocalize a variety of regulatory molecules involved in signal transduction and gene regulation. The stimulation of cells with soluble polypeptide factors leads to rapid changes in cell shape and microfilament component organization. In addition, this stimulation also activates the (...) phosphoinositide signaling pathway. Recently, a linkage between actin‐binding proteins and the phosphoinositide signaling pathway, was discovered. It is Suggested that by the association with the second messenger system, and/or by controlling the localization of regulatory molecules, the cytoskeleton may regulate gene expression. (shrink)

G protein‐coupled receptors (GPCRs) constitute the largest family of transmembrane proteins and play a crucial role in regulating diverse cellular functions. They transmit their signaling via binding to intracellular signal transducers and effectors, such as G proteins, GPCR kinases, and β‐arrestins. To influence specific GPCR signaling behaviors, β‐arrestins recruit effectors to form larger signaling complexes. Intriguingly, they facilitate divergent functions for the binding to different receptors. Recent studies relying on advanced structural approaches, novel biosensors and interactome (...) analyses bring us closer to understanding how this specificity is achieved. In this article, we share our hypothesis of how active GPCRs induce specific conformational rearrangements within β‐arrestins to reveal distinct binding interfaces, enabling the recruitment of a subset of effectors to foster specialized signaling complexes. Furthermore, we discuss methods of how to comprehensively assess β‐arrestin conformational states and present the current state of research regarding the functionality of these multifaceted scaffolding proteins. (shrink)

The extracellular domains of several integral membrane proteins are released from the cell surface by a group of enzymes known as “sheddases” through a process called “ectodomain shedding”. Because many transmembrane growth and differentiation factors, including members of the epidermal growth factor (EGF) family that play a crucial role in development, require ectodomain shedding for proper action in vivo, proteolysis is now viewed as a regulatory mechanism in the developing embryos. Two recent reports by Zhao et al. provide evidence (...) for the role of cell surface proteolysis by an ADAM (a disintegrin and metalloprotease) in the development of murine lung.(1,2) Inhibition of tumor necrosis factor‐α converting enzyme (TACE, ADAM17) by the hydroxamic acid‐based metalloprotease inhibitor (TAPI), (1) or a targeted mutation in Zn2+‐binding domain of TACE, (2) disrupts two essential epithelial functions in lung development: branching morphogenesis and cytodifferentiation. Evidence for the role of ADAMs as sheddases in development and growth factor signaling is discussed. BioEssays 24:8–12, 2002. © 2002 John Wiley & Sons, Inc. (shrink)

Most of the essential cellular components, like nucleic acids, lipids and sugars, are phosphorylated. The phosphate equilibrium in Escherichia coli is regulated by the phosphate (Pi) input from the surrounding medium. Some 90 proteins are synthesized at an increased rate during Pi starvation and the global control of the cellular metabolism requires cross‐talk with other regulatory mechanisms. Since the Pi concentration is normally low in E. coli's natural habitat, these cells have devised a mechanism for synthesis of about 15 proteins (...) to accomplish two specific functions: transport of Pi and its intracellular regulation. The synthesis of these proteins is controlled by two genes (the phoB‐phoR operon), involving both negative and positive functions. PhoR protein is a histidine protein kinase, induced in Pi starvation and is a transmembrane protein. It phosphorylates the regulator protein PhoB which is also Pi starvation‐induced. The PhoB phosphorylated form binds specifically to a DNA sequence of 18 nucleotides (the pho Box), which is part of the promoters of the Pho genes. The genes controlled by phoB constitute the Pho regulon.The repression of phoA (the gene encoding alkaline phosphatase) by high Pi concentrations in the medium requires the presence of an intact Pst operon (pstS, pstC, pstA, pstB and phoU) and phoR. The products of pstA and pstC are membrane bound, whereas the product of pstS is periplasmic and PstB and PhoU proteins are cytoplasmic. The function of the PhoU protein may be regulated by cofactor nucleotides and may be involved in signaling the activation of the regulon via PhoR. (shrink)

Chemotaxis and thermotaxis in Caenorhabditis elegans are based on the chemical senses (smell and taste) and the thermal sense, respectively, which are important for the life of the animal. Laser ablation experiments have allowed identification of sensory neurons and some interneurons required for these senses. Many mutants that exhibit various abnormalies have been isolated and analyzed. These studies have predicted novel signaling pathways whose components include a putative odorant specific transmembrane receptor (ODR‐10) and a cyclic nucleotide‐gated channel (TAX‐4/TAX‐2) (...) functioning in taste and thermosensation as well as in smell. The emerging picture of the mechanisms of sensory transduction in C. elegans seems to be basically similar to what is known of visual and olfactory sensory transduction in vertebrates. Thus, molecular and cellular analyses of chemotaxis and thermotaxis in C. elegans have proved useful and will continue to provide significant implications for the molecular basis of sensory systems in higher animals. (shrink)

Cell membranes experience frequent stretching and poking: from cytoskeletal elements, from osmotic imbalances, from fusion and budding of vesicles, and from forces from the outside. Are the ensuing changes in membrane tension localized near the site of perturbation, or do these changes propagate rapidly through the membrane to distant parts of the cell, perhaps as a mechanical mechanism of long‐range signaling? Literature statements on the timescale for membrane tension to equilibrate across a cell vary by a factor of ≈106. (...) This study reviews and discusses how apparently contradictory findings on tension propagation in cells can be evaluated in the context of 2D hydrodynamics and poroelasticity. Localization of tension in the cell membrane is likely critical in governing how membrane forces gate ion channels, set the subcellular distribution of vesicle fusion, and regulate the dynamics of cytoskeletal growth. Furthermore, in this study, it is proposed that cells can actively regulate the degree to which membrane tension propagates by modulating the density and arrangement of immobile transmembrane proteins. Also see the video abstract here https://youtu.be/T6K7AIAqqBs. (shrink)

Three recent reports (1–3) identify two genes, thick veins (tkv) and saxophone (sax), which encode serine/threonine transmembrane proteins that act as receptors for mediating different aspects of the Drosophila TGF‐β‐related signal, dpp. tkv is required for patterning the entire embryonic dorsal region, while sax is required for patterning only amnioserosa, the dorsalmost cell fates. dpp signaling in other developmental processes again requires both tkv and sax, but to differing degrees. tkv and sax, encode type I receptors, which appear (...) to directly bind ligand, unlike what has been observed for other type I receptors. (shrink)

Heterotrimeric G proteins, consisting of α, β, and γ subunits, couple ligand-bound seven transmembrane domain receptors to the regulation of effector proteins and production of intracellular second messengers. G protein signaling mediates the perception of environmental cues in all higher eukaryotic organisms, including yeast, Dictyostelium, plants, and animals. The nematode Caenorhabditis elegans is the first animal to have complete descriptions of its cellular anatomy, cell lineage, neuronal wiring diagram, and genomic sequence. In a recent paper, Jansen et al.(1) (...) used sequence searches of the C. elegans genome database to identify all heterotrimeric G protein genes (20 Gα, 2 Gβ, 2 Gγ). C. elegans encodes one ortholog of each of the four Gα classes found in metazoans and 16 new Gα genes. The orthologous genes are widely expressed, whereas 14 of the divergent Gα genes are almost exclusively expressed in sensory neurons where they may regulate perception and chemotaxis.BioEssays 21:713–717, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

Heterotrimeric G proteins, consisting of α, β, and γ subunits, couple ligand-bound seven transmembrane domain receptors to the regulation of effector proteins and production of intracellular second messengers. G protein signaling mediates the perception of environmental cues in all higher eukaryotic organisms, including yeast, Dictyostelium, plants, and animals. The nematode Caenorhabditis elegans is the first animal to have complete descriptions of its cellular anatomy, cell lineage, neuronal wiring diagram, and genomic sequence. In a recent paper, Jansen et al.(1) (...) used sequence searches of the C. elegans genome database to identify all heterotrimeric G protein genes (20 Gα, 2 Gβ, 2 Gγ). C. elegans encodes one ortholog of each of the four Gα classes found in metazoans and 16 new Gα genes. The orthologous genes are widely expressed, whereas 14 of the divergent Gα genes are almost exclusively expressed in sensory neurons where they may regulate perception and chemotaxis.BioEssays 21:713–717, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

Fertilization triggers cytoplasmic movements in the frog egg that lead in mysterious ways to the stabilization of β‐catenin on the dorsal side of the embryo. The novel Huluwa (Hwa) transmembrane protein, identified in China, is translated specifically in the dorsal side, acting as an egg cytoplasmic determinant essential for β‐catenin stabilization. The Wnt signaling pathway requires macropinocytosis and the sequestration inside multivesicular bodies (MVBs, the precursors of endolysosomes) of Axin1 and Glycogen Synthase Kinase 3 (GSK3) that normally destroy (...) β‐catenin. In Xenopus, the Wnt‐like activity of GSK3 inhibitors and of Hwa mRNA can be blocked by brief treatment with inhibitors of membrane trafficking or lysosomes at the 32‐cell stage. In dorsal blastomeres, lysosomal cathepsin is activated and intriguing MVBs surrounded by electron dense vesicles are formed at the 64‐cell stage. We conclude that membrane trafficking and lysosomal activity are critically important for the earliest asymmetries in vertebrate embryonic development. (shrink)

Here we review concepts related to an ensemble description of G-protein-coupled receptors. The ensemble is characterized by both inactive and active states, whose equilibrium populations and exchange rates depend sensitively on ligand, environment, and allosteric factors. This review focuses on the adenosine A2 receptor, a prototypical class A GPCR. 19F Nuclear Magnetic Resonance studies show that apo A2AR is characterized by a broad ensemble of conformers, spanning inactive to active states, and resembling states defined earlier for rhodopsin. In keeping with (...) ideas associated with a conformational selection mechanism, addition of agonist serves to allosterically restrict the overall degrees of freedom at the G protein binding interface and bias both states and functional dynamics to facilitate G protein binding and subsequent activation. While the ligand does not necessarily “induce” activation, it does bias sampling of states, increase the cooperativity of the activation process and thus, the lifetimes of functional activation intermediates, while restricting conformational dynamics to that needed for activation. GPCRs represent a ubiquitous class of transmembrane receptors, responsible for cell signaling and cell homeostasis. Their activation gives rise to conformational changes that allow the receptor to engage downstream partners. Activation can be thought of in terms of a free energy landscape associated with distinct conformers, responsible for the process. Here, the action of ligands is seen to alter this landscape by enabling transitions between key intermediates. (shrink)

Mechanical pain sensing, adipogenesis, and STING‐dependent innate immunity seem three distinct biological processes without substantial relationships. Intriguingly, TMEM120A, a transmembrane protein, has been shown to detect mechanical pain stimuli as a mechanosensitive channel, contribute to adipocyte differentiation/function by regulating genome organization and promote STING trafficking to active cellular innate immune response. However, the role of TMEM120A as a mechanosensitive channel was challenged by recent studies which cannot reproduce data supporting its role in mechanosensing. Furthermore, the molecular mechanism by which (...) TMEM120A contributes to adipocyte differentiation/function and promotes STING trafficking remains elusive. In this review, we discuss these multiple proposed functions of TMEM120A and hypothesize the molecular mechanism underlying TMEM120A's role in fatty acid metabolism and STING signaling. (shrink)

Wnt proteins form a family of secreted signaling proteins that play a key role in various developmental events such as cell differentiation, cell migration, cell polarity and cell proliferation. It is currently thought that Wnt proteins activate at least three different signaling pathways by binding to seven transmembrane receptors of the Frizzled family and the co-receptor LRP6. Despite our growing knowledge of intracellular components that mediate a Wnt signal, the molecular events at the membrane have remained rather (...) unclear. Now several publications1-4 indicate that Frizzled receptors are G-protein coupled and kinases were identified that phosphorylate the co-receptor LRP6. These data deepen our understanding of Wnt-mediated signal transduction and provide more insight into how specificity may be achieved. BioEssays 28: 339–343, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Neurobiology studies mechanisms of cell signalling. A key question is how cells recognise specific signals. In this context, olfaction has become an important experimental system over the past 25 years. The olfactory system responds to an array of structurally diverse stimuli. The discovery of the olfactory receptors (ORs), recognising these stimuli, established the olfactory pathway as part of a greater group of signalling mechanisms mediated by G-protein-coupled receptors (GPCRs). GPCRs are the largest protein family in the mammalian genome and involved (...) in numerous fundamental physiological processes. The OR family exhibits two characteristics that make them an excellent model system to understand GPCRs: its size and the structural diversity of its members. Research on the OR binding site investigates what amino acid sequences determine the receptor-binding capacity. This promises a better understanding of how the basic genetic makeup of GPCRs relates to their diversification in ligand-binding capacities. (shrink)

Major hallmarks of Alzheimer's disease include brain deposition of the amyloid-beta peptide , which is proteolytically cleaved from a large Abeta precursor protein by beta and gamma- secretases. A transmembrane aspartyl protease, beta-APP cleaving enzyme , has been recognized as the beta-secretase. We review the structure and function of the BACE1 protein, and of 4129 bp of the 5'-flanking region sequence of the BACE1 gene and its interaction with various transcription factors involved in cell signaling. The promoter region (...) and 5'-untranslated region contain multiple transcription factor binding sites, such as AP-1, CREB and MEF2. A 91 bp fragment is the shortest region with significant reporter gene activity and constitutes the minimal promoter element for BACE1. The BACE1 promoter contains six unique functional domains and three structural domains of increasing sequence complexity as the "ATG" start codon is approached. Notably, the BACE1 gene promoter contains basal regulatory elements, inducible features and sites for regulation by various important transcription factors. Herein, we also discuss and speculate how the interaction of these transcription factors with the BACE1 promoter can modulate synaptic plasticity, neuronal apoptosis and oxidative stress, which are pertinent to the pathogenesis and progression of AD. (shrink)

‘Virtue signaling’ is the practice of using moral talk in order to enhance one’s moral reputation. Many find this kind of behavior irritating. However, some philosophers have gone further, arguing that virtue signaling actively undermines the proper functioning of public moral discourse and impedes moral progress. Against this view, I argue that widespread virtue signaling is not a social ill, and that it can actually serve as an invaluable instrument for moral change, especially in cases where moral (...) argument alone does not suffice. Specifically, virtue signaling can change the broader public’s social expectations, which can in turn motivate the adoption of new, positive social norms. I also argue that the reputation-seeking motives underlying virtue signaling impose important constraints on virtue signalers’ behavior, which serve to keep the worst excesses of virtue signaling in check. (shrink)

Why do people share or publicly engage with fake stories? Two possible answers come to mind: (a) people are deeply irrational and believe these stories to be true; or (b) they intend to deceive their audience. Both answers presuppose the idea that people put the stories forward as true. But I argue that in some cases, these outlandish (yet also very popular) stories function as signals of one's group membership. This signaling function can make better sense of why, despite (...) their unusual nature or lack of a factual basis, some of these stories are so widespread. (shrink)

Natural languages are compositional in that the meaning of complex expressions depends on those of the parts and how they are put together. Here, I ask the following question: why are languages compositional? I answer this question by extending Lewis–Skyrms signaling games with a rudimentary form of compositional signaling and exploring simple reinforcement learning therein. As it turns out: in complex worlds, having compositional signaling helps simple agents learn to communicate. I am also able to show that (...) learning the meaning of a function word, once meanings of atomic words are known, presents no difficulty. (shrink)

Ethological theories usually attribute semantic content to animal signals. To account for this fact, many biologists and philosophers appeal to some version of teleosemantics. However, this picture has recently came under attack: while mainstream teleosemantics assumes that representational systems must cooperate, some biologists and philosophers argue that in certain cases signaling can evolve within systems lacking common interest. In this paper I defend the standard view from this objection.

The signaling theory of religion has many claimed virtues, but these are not necessarily all realizable at the same time. Modeling choices involve trade-offs, and the available options here have not traditionally been well understood. This paper offers an overview of signaling theory relevant to the signaling theory of religion, arguing for a narrow, “core” reading of it. I outline a broad taxonomy of the choices on offer for signaling models, and examples of how previous and (...) potential approaches to modeling religious signaling meet or fail to meet the initial promise of the theory. A pluralist approach to religious signaling seems possible, but this would require a high level of detail and specificity with respect to both formal models and target systems. (shrink)

Tosi and Warmke discuss cases where the speaker intends for the audience to take their expressions as evidence of good moral character. However, another possibility exists that similarly exploits the social communicative architecture. A contribution to public moral discourse may also attempt to strut by demonstrating evidence of bad moral character, by purposely failing to meet the evaluative standards of its audience—or, paradigmatically for my purposes, a particular section of its actual or notional audience. I call this kind of communication (...) vice signaling. On their face, virtue signaling and vice signaling may seem to be opposites, since the labels imply that they are signaling opposite things. But certain cases of vice signaling are in fact also cases of virtue signaling. These are the cases where someone flaunts the standards of an out-group in order to demonstrate solidarity, seriousness, or some other virtue to their in-group. In this paper I attempt to describe these cases and point out the moral risks and opportunities they present. (shrink)

The paper offers a model of Kant's claim that unity of consciousness entails objectivity of experience. This claim has nothing especially to do with thought, language or the categories but is a general truth about arbitrary signaling systems of the sort modeled in the paper. In conclusion I draw some consequences for various forms of idealism.

We consider how human subjects establish signaling conventions in the context of Lewis-Skyrms signaling games. These experiments involve games where there are precisely the right number of signal types to represent the states of nature, games where there are more signal types than states, and games where there are fewer signal types than states. The aim is to determine the conditions under which subjects are able to establish signaling conventions in such games and to identify a learning (...) dynamics that approximates how they succeed when they do. Our results suggest that human agents tend to use a win-stay/lose-shift with inertia dynamics to establish conventions in such games. We briefly consider the virtues and vices of this low-rationality dynamics. (shrink)

Costly signaling theories of religion contend that religious belief and behaviors function as costly signals of cooperative intent. Such signals are evolvable because they allow likely cooperators to find one another, while excluding potential cheats or free riders that would be unwilling to pay the price associated with sending the signal. As a result, under the right conditions, religious costly signaling can emerge as an evolutionary stable strategy. However, reliability certifying costly signaling can evolve and stabilize only (...) when certain necessary conditions are satisfied. In this paper we argue that current versions of the theory do not adequately demonstrate that these conditions are met. (shrink)

Virtue signaling—using public moral discourse to enhance one’s moral reputation—is a familiar concept. But, what about profile pictures framed by “Vaccines work!”? Or memes posted to anti-vaccine groups echoing the group’s view that “Only sheep believe Big Pharma!”? These actions don’t express moral views—both claims are empirical (if imprecise). Nevertheless, they serve a similar purpose: to influence the judgments of their audience. But, where rainbow profiles guide their audience to view the agent as morally good, these acts guide their (...) audience to view the agent as epistemically good. They are instances of epistemic virtue signaling. The first goal of this paper is to offer an account of epistemic virtue signaling. I argue that epistemic virtue signaling occurs through both behavioral and propositional signals, and serves purposes similar to those of moral virtue signaling across a wide variety of discourses. The second is to show that there is much work for this concept to do. In particular, this concept illuminates a double bind faced by those who suffer from and seek to overcome testimonial injustice. I close by demonstrating how this double bind arises in the dissolution of medical autonomy, focusing on the care gap faced by pregnant women of color in the United States today, as compared with their white counterparts. (shrink)

An extensive body of research documents that women experience a motherhood penalty at work whereas men experience a fatherhood premium. Yet much of this work presupposes that employers are aware of a worker’s parental status. Given the different consequences that parenthood has on outcomes such as pay and promotions, it is conceivable that men and women may deploy their status as parents differently when interacting with employers. Drawing on in-depth interviews with a racially diverse sample, this article examines how mothers (...) and fathers working in the service sector use their parental status when negotiating work and child care responsibilities. Mothers, particularly black mothers, were less likely to openly discuss their children at work. In some cases, women purposefully concealed from their employers the fact that they were mothers or found other ways of signaling their commitment to their jobs. Fathers, on the other hand, were more likely to discuss their children with their employers and overwhelmingly characterized their managers as understanding of their parenting obligations. Together, these findings help us understand how mothers and fathers navigate the consequences of parenthood in the workplace and add nuance to previous studies of motherhood penalties and fatherhood premiums. (shrink)

In game-theoretic signaling models, evolution tends to favor perfectly precise signaling systems, but in the natural world communication is almost always imprecise. I argue that standard explanations for this discrepancy are only partially sufficient, and I show that communication is often ambiguous because signal senders take advantage of context sensitivity. As evidence, I make two additions to the signaling model: a cost for more complex signaling strategies and the ability to combine information in signals with independent (...) information. Analysis and simulation of the altered model shows that it leads to the predicted outcome of evolution favoring ambiguous signaling. (shrink)

What signals do firms in emerging economies send to stakeholders when they adopt corporate social responsibility practices? We argue that in emerging economies, firms that adopt CSR practices positively signal investors that their firms have superior capabilities for filling institutional voids. From an institution-based view, we hypothesize that the institutional environment moderates the signaling effect of CSR on a firm’s financial performance. Based on a sample of firms from ten Asian emerging economies, we find a positive relationship between CSR (...) practices and financial performance. This positive relationship is stronger in the less developed capital market than in the more developed one. The financial benefits of CSR practices are also more salient in the low information diffusion market than in the high one. We emphasize that signaling theory and the institution-based view can jointly contribute to the CSR literature. (shrink)

What are the functional units of the brain? If the function of the brain is to process information-carrying signals, then the functional units will be the senders and receivers of those signals. Neurons have been the default candidate, with action potentials as the signals. But there are alternatives: synapses fit the action potential picture more cleanly, and glial activities (e.g., in astrocytes) might also be characterized as signaling. Are synapses or nonneuronal cells better candidates to play the role of (...) functional units? Will informational signaling still be the best model for brain function if we move beyond the neuron doctrine? (shrink)

Between 300,000 and 250,000 years ago early humans in Africa and Eurasia began to use durable material substances and objects as media for signaling. Initially material signals were confined to ochre and other pigments, but over time objects such as beads were also added as technologies for sending messages. Changes in the types of materials used, their durability and costs, and the contexts of their disposal indicate a series of transitions in how early humans employed signaling media. (...) class='Hi'>Signaling theory from biology suggests that shifts in technologies over the course of the Pleistocene reflect problems in coordinating action and resolving conflicts within increasingly large and internally differentiated societies. (shrink)

Signaling of relations is an open question in rhetorical structure theory. Discourse markers are the unmistakable signals of a relation. However, it may be argued that all relations – and not only those involving discourse markers – are signaled in some way. Based on this assumption, this article focuses on two causal relations, ‘Cause’ and ‘Result’, working on an RST double-annotated corpus in Spanish. The main objectives are to identify different signals of Cause and Result relations and to evaluate (...) the ambiguity resulting from those signals. Results demonstrate that a) almost all Cause and Result relations on the corpus are signaled; b) each signal obtains differentiated annotation agreements; and c) patterns of annotation disagreement are grounded in the nature of the signal and not in the relations’ semantic features. (shrink)

An important finding of the game theoretic research on signaling games is the insight that under many circumstances, a signal obtains credibility by incurring costs to the sender. Therefore it seems questionable whether or not cheap talk—signals that are not payoff relevant—can serve to transmit information among rational agents. This issue is non-trivial in strategic interactions where the preferences of the players are not aligned. Researchers like Crawford & Sobel, Rabin, and Farrell demonstrated, however, that even in the case (...) of partially divergent interests, cheap talk may be informative. They assume that signals have an exogenously given meaning that is common knowledge between the players, and they explore the conditions under which such a signal is credible. This discussion has obvious relevance to the program of Gricean pragmatics in linguistics. According to Grice’s "Cooperative Principle”, this research tradition only considers scenarios where the interests of the players are aligned. Nevertheless, the assumption of differential signaling costs introduces an element of non-aligned interests. The present paper proposes a framework that combines these two research strands. Using an inference protocol of iterated best response, it gives a recipe for how the interlocutors derive rationalizable strategies from exogeneously given "literal” meanings of signals. No special assumptions about the alignment of interests or signaling costs are made. After introducing the formal model, the paper sketches several applications of this model to problems in linguistic pragmatics, like scalar implicatures, the division of pragmatic labor, and the interpretation of measure terms. (shrink)

Special relativity is said to prohibit faster-than-light (superluminal) signaling, yet controversy regularly arises as to whether this or that physical phenomenon violates the prohibition. I argue that the controversy is a result of a lack of clarity as to what it means to ‘signal’, and I propose a criterion. I show that according to this criterion, superluminal signaling is not prohibited by special relativity.

Mechanical stimulation has a critical role in the development and maintenance of the skeleton. This function requires the perception of extracellular stimuli as well as their conversion into intracellular biochemical responses. This process is called mechanotransduction and is mediated by a plethora of molecular events that regulate bone metabolism. Indeed, mechanoreceptors, such as integrins, G protein‐coupled receptors, receptor protein tyrosine kinases, and stretch‐activated Ca2+ channels, together with their downstream effectors coordinate the transmission of load‐induced signals to the nucleus and the (...) expression of bone‐related genes. During the past decade, scientists have gained increasing insight into the molecular networks implicated in bone mechanotransduction. In the present paper, we consider the major signaling cascades and transcription factors that control bone and cartilage mechanobiology and discuss the influence of the mechanical microenvironment on the determination of skeletal morphology. (shrink)

We employ the Social Signaling Model and life history of a Western Dani big-man, Tibenuk, to analyze a neglected curiosity in the career of the big-man type. The big-man is renowned as an economic entrepreneur, the master of material displays. In New Guinea, however, big-men had invariably first gained fame and some influence as eminent warriors. The SSM accounts for this two-part career path by proposing that small-scale social organization rests on honest, competitive signaling of individual and collective (...) fighting strength, with leaders being those who excel in these contests. The performances for which big-men are already known, conspicuous ceremonial displays, broadcast this strength indirectly. Explicitly conceptualized as symbolic fighting, they constituted indexical proxies for their sponsors’ individual and collective willingness and ability to fight. Success on the battlefield, though, signaled fighting strength more directly. Men therefore had to demonstrate strength on both the battlefield and the ceremonial ground if they were to become big-men. This was Tibenuk’s achievement. When he was young and at his physical peak, he demonstrated outstanding capability in war. War is a young man’s game, however, and as his physical capacities waned, he shifted to politics, an older man’s game, honing his political talents and developing extensive political networks that allowed him to sponsor massive pig feasts, the principal form of conspicuous ceremonial display. Tibenuk’s career also reveals synergies between warrior and political talents that hitherto have been overlooked in big-man analysis. (shrink)

The branch of evolutionary theory known as signaling theory attempts to explain various forms of communication. Social scientists have explained many traditional rituals as forms of communication that promote cooperative social relationships among participants. Both evolutionists and social scientists have realized the importance of trust for the formation and maintenance of cooperative social relationships. These factors have led to attempts to apply signaling theory to traditional cultural rituals in various ways. This paper uses the traditional ritual of mumming (...) in small Newfoundland fishing villages to evaluate alternative hypotheses about the connection between rituals, communication, trust, and cooperation. Mumming is found to be most consistent with the hypothesis that it is a ritual of trust wherein participants take a specific type of risk: the risk of harm at the hands of other participants. Individuals who take this risk actively signal their trust. Conversely, individuals who restrain themselves from inflicting harm on other participants actively signal their trustworthiness. (shrink)

Cooption and modularity are informative concepts in evolutionary developmental biology. Genes function within complex networks that act as modules in development. These modules can then be coopted in various functional and evolutionary contexts. Hormonal signaling, the main focus of this review, has a modular character. By regulating the activities of genes, proteins and other cellular molecules, a hormonal signal can have major effects on physiological and ontogenetic processes within and across tissues over a wide spatial and temporal scale. Because (...) of this property, we argue that hormones are frequently involved in the coordination of life history transitions (LHTs) and their evolution (LHE). Finally, we promote the usefulness of a comparative, non-model system approach towards understanding how hormones function and guide development and evolution, highlighting thyroid hormone function in echinoids as an example. BioEssays 27:64–75, 2005. © 2004 Wiley Periodicals, Inc. (shrink)

Voices on the political right have long claimed that the welfare state ought to be kept small, and that charities can take over many of the tasks involved in helping those at the bottom of society. The arguments in favor of this claim are controversial, but even if they are accepted at face value the policy proposal remains problematic. For the proposal presupposes that charities would, in fact, be able to raise enough money to provide adequate help to those in (...) need, and therefore assumes that charities are able to very significantly increase the number and/or size of donations they receive. We argue that there are good reasons for doubting that charities will be able to do this. Our argument turns on the fact that the most powerful strategy for eliciting donations—namely, allowing donors to use their donation to signal their pro-sociality—has an inbuilt upper limit. If too much emphasis is placed on the signaling opportunities donating to charity provides, donating no longer functions as an effective signal and the motivation to donate declines. (shrink)

Recent findings in several organ systems show that cytoneme‐mediated signaling transports signaling proteins along cellular extensions and targets cell‐to‐cell exchanges to synaptic contacts. This mechanism of paracrine signaling may be a general one that is used by many (or all) cell types in many (or all) organs. We briefly review these findings in this perspective. We also describe the properties of several signaling systems that have previously been interpreted to support a passive diffusion mechanism of (...) class='Hi'>signaling protein dispersion, but can now be understood in the context of the cytoneme mechanism.Also watch the Video Abstract. (shrink)

Cognitive Science, Volume 45, Issue 11, November 2021.

The evolutionarily conserved Notch signaling pathway regulates a broad spectrum of cell fate decisions and differentiation processes during fetal and postnatal life. It is involved in embryonic organogenesis as well as in the maintenance of homeostasis of self‐renewing systems. In this article, we review the role of Notch signaling in the hematopoietic system with particular emphasis on lymphocyte development and highlight the similarities in Notch function between Drosophila and mammalian differentiation processes. Recent studies indicating that aberrant NOTCH (...) class='Hi'>signaling is frequently linked to the induction of T leukemia in humans will also be discussed. BioEssays 27:1117–1128, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

A firm’s social performance can shape the impressions of key stakeholders, such as employees, customers, suppliers, and investors, that influence subsequent decision making and relationships to the firm. To test this notion, we examine how a firm’s public recognition for exemplary social performance can serve as a positive signal of the firm’s business performance to shareholders. We conduct an event study of firms named to Working Mothermagazine’s list of “Most Family- Friendly Companies” for the first time between 1989 and 1994. (...) We find statistically significant, positive, abnormal returns for such firms, in particular for firms whose shares are traded on the NASDAQ stock exchange. (shrink)

Focal adhesion kinase (FAK) is a nonreceptor protein‐tyrosine kinase implicated in controlling cellular responses to the engagement of cell‐surface integrins, including cell spreading and migration, survival and proliferation. Aberrant FAK signaling may contribute to the process of cell transformation by certain oncoproteins, including v‐Src. Progress toward elucidating the events leading to FAK activation following integrin‐mediated cell adhesion, as well as events downstream of FAK, has come through the identification of FAK phosphorylation sites and interacting proteins. A signaling partnership (...) is formed between FAK and Src‐family kinases, leading to tyrosine phosphorylation of FAK and associated ‘docking’ proteins Cas and paxillin. Subsequent recruitment of proteins containing Src homology 2 domains, including Grb2 and c‐Crk, to the complex is likely to trigger adhesion‐induced cellular responses, including changes to the actin cytoskeleton and activation of the Ras‐MAP kinase pathway. (shrink)

I introduce an extension of the Lewis-Skyrms signaling game, analysed from a dynamical perspective via simple reinforcement learning. In Lewis’ (Convention, Blackwell, Oxford, 1969) conception of a signaling game, salience is offered as an explanation for how individuals may come to agree upon a linguistic convention. Skyrms (Signals: evolution, learning & information, Oxford University Press, Oxford, 2010a) offers a dynamic explanation of how signaling conventions might arise presupposing no salience whatsoever. The extension of the atomic signaling (...) game examined here—which I will refer to as a salience game—introduces a variable parameter into the atomic signaling game which allows for degrees of salience, thus filling in the continuum between Skyrms’ and Lewis’ models. The model does not presuppose any salience at the outset, but illustrates a process by which accidentally evolved salience is amplified, to the benefit of the players. It is shown that increasing degrees of salience allow populations to avoid sub-optimal pooling equilibria and to coordinate upon conventions more quickly. (shrink)