BRICS has philosophical significance. It creates new pressure on cross-cultural skill. This is analysed here as requiring transduction: a variety of defeasible practical reasoning. This replaces a simplistic model of the relation between knowledge and action with a more realistic and contemporary model. The transduction format has utility in cross-cultural training.

Cellular 3D structures, for example, organoids, are an excellent model for studying and developing treatments for various diseases, including hereditary ones. Therefore, they are increasingly being used in biomedical research. From the point of view of safety and efficacy, recombinant adeno‐associated viral (rAAV) vectors are currently most in demand for the delivery of various transgenes for gene replacement therapy or other applications. The delivery of transgenes using rAAV vectors to various types of organoids is an urgent task, however, it is (...) associated with a number of problems that are discussed in this review. Cellular heterogeneity and specifics of cultivation of 3D structures determine the complexity of rAAV delivery and are sometimes associated with low transduction efficiency. This review surveys the main ways to solve emerging problems and increase the efficiency of transgene delivery using rAAVs to organoids. A clear understanding of the stage of development of the organoid, its cellular composition and the presence of surface receptors will allow obtaining high levels of organoid transduction with existing rAAV vectors. (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)

The integrins are receptors for proteins of the extracellular matrix, both providing a physical link to the cytoskeleton and transducing signals from the extracellular matrix. Activation of integrins leads to tyrosine and serine phosphorylation of a number of proteins, elevation of cytosolic calcium levels, cytoplasmic alkalinization, changes in phospholipid metabolism and, ultimately, changes in gene expression. The recently discovered focal adhesion kinase localizes to focal contacts, which are sites of integrin clustering, and focal adhesion kinase can physically associate with integrins (...) in vitro. As integrins lack intrinsic catalytic activity, focal adhesion kinase is a candidate for a signaling molecule that is recruited by integrins in order to trigger the generation of intracellular second messengers. Thus, focal adhesion kinase may play a central role in signal transduction through integrins. (shrink)

This article is one in a series that develops the concept of logomachy. Logomachy is a philosophy of semantics or sense that takes into consideration the thermodynamic status of things in the world (their quamity). In particular, this article, looks at Gilbert Simondon’s claim that the laws of thought (Identity, Contradiction and the Excluded Middle) do not hold once certain thermodynamic states such as metastability (in between stability and instability) are taken into account. This article formulates, through a method I (...) term transduction (the mutual development of concepts between domains), novel logical laws that fit more adequately the way things thermodynamically are in the world. To do this, the article turns to the presocratic philosopher Heraclitus to rethink the logos as a conflictual site of meaning where things, and their capacity to make-sense, is conditioned by energetic investment, where difference is the condition of sameness. (shrink)

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)

Pains are subject to obvious, well-documented, and striking top-down influences. This is in stark contrast to visual perception, where the debate over cognitive penetrability tends to revolve around fairly subtle experimental effects. Several authors have recently taken up the question of whether top-down effects on pain count as cognitive penetrability, and what that might show us about traditional debates. I review some of the known mechanisms for top-down modulation of pain, and suggest that it reveals an issue with a relatively (...) neglected part of the cognitive penetrability literature. Much of the debate inherits Pylyshyn’s stark contrast between transducers and cognition proper. His distinction grew out of his running fight with Gibson, and is far too strong to be defensible. I suggest that we might therefore view top-down influences on pain as a species of transducer calibration. This provides a novel but principled way to distinguish between several varieties of top-down effect according to their architectural features. (shrink)

Local deterministic string-to-string transductions arise in natural language processing (NLP) tasks such as letter-to-sound translation or pronunciation modeling. This class of transductions is a simple generalization of morphisms of free monoids; learning local transductions is essentially the same as inference of certain monoid morphisms. However, learning even a highly restricted class of morphisms, the so-called fine morphisms, leads to intractable problems: deciding whether a hypothesized fine morphism is consistent with observations is an NP-complete problem; and maximizing classification accuracy of the (...) even smaller class of alphabetic substitution morphisms is APX-hard. These theoretical results provide some justification for using the kinds of heuristics that are commonly used for this learning task. (shrink)

Many bacteria that cause disease have the capacity to enter into and live within eukaryotic cells such as epithelial cells and macrophages. The mechanisms used by these organisms to achieve and maintain this intracellular lifestyle vary considerably, but most mechanisms involve subversion and exploitation of host cell functions. Entry into non‐phagocytic cells involves triggering host signal transduction mechanisms to induce rearrangement of the host cytoskeleton, thereby facilitating bacterial uptake. Once inside the host cell, intracellular pathogens either remain within membrane (...) bound inclusions or escape to the cytoplasm. Those living in the cytoplasm can further pirate the host actin system, using actin as a mechanism to facilitate movement within and between host cells. Organisms remaining within the vacuole have specialized mechanisms for intracellular survival and growth which involve additional communication with the host cell. Some of the processes involved in the various steps of facultative intracellular parasitism are discussed in the context of subverting the host cell cytoskeleton and signal transduction pathways for bacterial benefit. (shrink)

Can someone be reasonable or justified in accepting a specific moral judgment not based on the prior acceptance of a general exceptioness moral principle, where acceptance of a general principle might be tacit or implicit and might not be expressible in language? This issue is an instance of a wider issue about direct or transductive inference. Developments in statistical learning theory show that such an inference can be more effective than alternative methods using inductive generalization and so can be reasonable. (...) This result carries over to moral transduction, although it is a difficult empirical issue whether people actually engage in any sort of transduction, including moral transduction. (shrink)

I reply to Stainton and Viger by pointing out that my “folieist” claim—that standard linguistic entities (“SLEs”) such as words and phonemes are illusions—would not have the calamitous consequences for linguistics that they fear. Talk of “a language” need only be understood as talk of an I‐language precisely as Chomskyans have proposed; and I reply to Adger by pointing out that, since SLEs are not generally describable as real, local physical phenomena, perception of them cannot be explained as any sort (...) of “transduction.” An intentionalist understanding of “representation of” is needed where mere transduction fails. (shrink)

Many abiotic and other signals are transduced in eukaryotic cells by changes in the level of free calcium via pumps, channels and stores. We suggest here that ion condensation should also be taken into account. Calcium, like other counterions, is condensed onto linear polymers at a critical value of the charge density. Such condensation resembles a phase transition and has a topological basis in that it is promoted by linear as opposed to spherical assemblies of charges. Condensed counterions are delocalised (...) and can diffuse in the so‐called near region along the polymers. It is generally admitted that cytoskeletal filaments, proteins colocalised with these filaments, protein filaments distinct from cytoskeletal filaments, and filamentous assemblies of other macromolecules, constitute an intracellular macromolecular network. Here we draw attention to the fact that this network has physicochemical characteristics that enable counterion condensation. We then propose a model in which the feedback relationships between the condensation/decondensation of calcium and the activation of calcium‐dependent kinases and phosphatases control the charge density of the filaments of the intracellular macromolecular network. We show how condensation might help mediate free levels of calcium both locally and globally. In this model, calcium condensation/decondensation on the macromolecular network creates coherent patterns of protein phosphorylation that integrate signals. This leads us to hypothesize that the process of ion condensation operates in signal transduction, that it can have an integrative role and that the macromolecular network serves as an integrative receptor. BioEssays 26:549–557, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The article explores the question of Gilbert Simondon’s (1924–1989) attitude to dialectics and the influence of G.W.F. Hegel’s philosophy on his theory of individuation. Simon­don’s philosophy is seen as a coherent system with its own method and original concep­tual apparatus, developed also in the course of a critical revision of Hegelian dialectics. It is noted that in a number of cases the French philosopher describes processes, connec­tions, relations as dialectical, in others as non-dialectical. The use of common terms (e.g. “abstract” (...) and “concrete”) is analyzed in order to discover the influence of Hegel’s ideas on Simondon’s philosophy. In addition to his dissertations, which are widely recog­nized internationally, lesser-known recent publications from the philosopher’s archive are also drawn upon. On the basis of these texts, it is shown that in his philosophy of techno­logy, in an attempt to disassociate himself from certain dialectical categories, including such essential ones as “negation”, “sublation”, and the triad “thesis – antithesis – synthe­sis”, he developed an approach to which he gave the name of analectic. Simondon’s con­cept of transduction is described, in which one can see the main difference between his understanding of the processes of change and development and that proposed by Hegel. At the same time, it is noted that although the three levels of technique (element, indi­vidual and ensemble) and the three “phases of being” (pre-individual, individual, trans­individual) are seen by Simondon as a transductive unity, in some aspects a dialectical relationship is maintained between them. It is concluded that at a superficial glance Si­mondon’s philosophy has little in common with Hegelian dialectics, but on closer exami­nation of the underlying foundations of Simondon’s approach it becomes apparent that it is implicit in it. (shrink)

An increasing number of studies indicate that changes in cytosolic free Ca2+ ([Ca2+]c) mediate specific types of signal transduction in plant cells. Modulation of [Ca2+]c is likely to be achieved through changes in the activity of Ca2+ channels, which catalyse passive influx of Ca2+ to the cytosol from extracellular and intracellular compartments. Voltage‐sensitive Ca2+ channels have been detected in the plasma membranes of algae, where they control membrane electrical properties and cell turgor. These channels are sensitive to 1,4‐dihydropyridines, which (...) in animal cells specifically affect one class of voltage‐regulated plasma membrane Ca2+ channel. Ca2+‐permeable channels with different pharmacological properties have been found in the plasma membrane of higher plants. Recent evidence suggests the existence of two discrete classes of Ca2+ channel co‐resident in the vacuolar membrane (tonoplast) of higher plants. The first is gated by inositol 1,4,5‐trisphosphate, and bears a number of similarities to its animal counterpart which is located in the endoplasmic reticulum (ER). The second tonoplast Ca2+ channel is voltage‐operated. However, the specific roles of these tonoplast channels in signal transduction have yet to be elucidated. (shrink)

Embryonic development and adult tissue homeostasis are controlled through activation of intracellular signal transduction pathways by extracellular growth factors. In the past, signal transduction has largely been regarded as a linear process. However, more recent data from large‐scale and high‐throughput experiments indicate that there is extensive cross‐talk between individual signaling cascades leading to the notion of a signaling network. The behavior of such complex networks cannot be predicted by simple intuitive approaches but requires sophisticated models and computational simulations. (...) The purpose of such models is to generate experimentally testable hypotheses and to find explanations for unexpected experimental results. Here, we discuss the need for, and the future impact of, mathematical models for exploring signal transduction in different biological contexts such as for example development. BioEssays 30:1110–1125, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

The regulatory NodD proteins of Rhizobium bacteria mediate the activation of a gene set responsible for symbiotic nodule formation by plant signal molecules. Here we discuss the signal recognition and gene activation properties of NodD and present a model summarizing the current knowledge on NodD action.

It makes sense to review these two books together since they both address the concept of semiotranslation, Dinda L. Gorlée extending her previous writings on the subject by adding intermedial intertextuality argued as 'transduction', and Douglas Robinson subjecting semiotranslation to a sustained critique before offering his own icotic position.In agreement with her previous publications, Gorlée rejects any notion of translation as a simple substitution of linguistic expressions. Instead, the translation process and its results are seen as non-symmetrical, forever changing (...) over time and between cultures. 'Translation' now encompasses a broad spectrum of transformations from intralingual paraphrase to intermedial... (shrink)

Insulin resistance is thought to be the primary defect in the pathophysiology of type 2 diabetes. Thus, understanding the cellular mechanisms of insulin action may contribute significantly to developing new treatments for this disease. Although the effects of insulin on glucose and lipid metabolism are well documented, gaps remain in our understanding of the precise molecular mechanisms of signal transduction for the hormone. One potential clue to understanding the unique cellular effects of insulin may lie in the compartmentalization of (...) signaling molecules and metabolic enzymes. We review this evidence, and speculate on how PI-3 kinase-independent and -dependent signaling pathways both diverge from the insulin receptor and converge at discrete targets to insure the specificity of insulin action. BioEssays 23:215–222, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Many experimental found footage films base their meanings and effects on an interaction between the figurative content of the image and its material-technological underpinnings. Can this interaction arise accidentally without artistic appropriation? A recently digitised film by the Czech cinema pioneer Jan Kříženecký, Opening Ceremony of the Čech Bridge (1908), presents such an exercise in accidental aesthetics. At one point, the horizontal and vertical trembling of the cinematograph – obtained from the Lumière brothers – translates into a trembling of the (...) figures on the bridge so precisely that the figurative and material spheres appear to cooperate towards a common aesthetic goal. To account for such phenomena, film theory, found footage filmmaking, and archival practice need to join forces with philosophy. More specifically, Gilbert Simondon's notion of transduction, a process based on the intersection of diverse realities within a domain, allows us to conceptualise the paradoxical interaction between the figurative and material dimensions and the unintentional meanings that arise out of it. Transduction enables the distribution of elements between these heterogeneous spheres while maintaining a certain stability within a system. In the case of archival films in which transduction occurs without prior intention or expectation, transduction can be foregrounded and prolonged. The connection between transduction and the “trembling meaning” of Opening Ceremony, understood within the wider context of camera instability in experimental found footage, will uncover the aesthetic potentialities held by the autonomous creativity of film matter and its interferences with the figurative content. (shrink)

Cytokine receptors fall into two basic classes: those with their own intrinsic protein tyrosine kinase (PTK) domain, and those lacking a PTK domain. Nonetheless, PTK activity plays a fundamental role in the signal transduction processes lying downstream of both classes of receptor. It now seems likely that many of those cytokine receptors that lack their own PTK domain use members of the JAK family of PTKs to propagate their intracellular signals. Moreover, the involvement of the JAK kinases in a (...) newly defined pathway which links membrane receptors directly to the activation of nuclear genes, via latent cytoplasmic transcription factors known as STATs (for Signal Transducers and Activators of Transcription), appears to be a theme common to cytokine receptors of both classes. (shrink)

Recent algorithmic technologies have challenged law’s anthropocentric assumptions. In this article, we develop a set of theoretical tools drawn from new materialisms and the philosophy of information to unravel the complex intra-actions between law and computer code. Accordingly, we first propose a framework for understanding the enmeshing of law and code based on a diffractive reading of Barad’s agential realism and Simondon’s theory of information. We argue that once law and code are understood as material entities that intra-act through in-formation, (...) the concept of transduction allows us to trace how they push each other towards change. After developing the theoretical tools, we deploy them to make sense of how law and code have changed in response to increasing automation of decision-making and the appearance of unexplainable artificial intelligence (AI) code. Thus, we employ a case study to trace transformations of the right to explanation under the European data protection regulations. This provides the backdrop for our account of how law transduces into code (and vice versa) and a proving ground for our framework. (shrink)

Phosphotyrosine phosphatases (PTPases) are the enzymes which remove phosphate groups from protein tyrosine residues. An enormous number of phosphatases have been cloned and sequenced during the past decade, many of which are expressed in haematopoietic cells. This review focuses on the biochemistry and cell biology of three phosphatases, the transmembrane CD45 and the cytosolic SH2‐domain‐containing PTPases SHP‐1 and SHP‐2, to illustrate the diverse ways in which PTPases regulate receptor signal transduction. The involvement of these and other PTPases has been (...) demonstrated in haematopoietic cell development, apoptosis, activation and non‐responsiveness. A common theme in the actions of many haematopoietic cell PTPases is the way in which they modulate the thresholds for receptor signalling, thereby regulating critical events in the positive and negative selection of lymphocytes. There is growing interest in haematopoietic PTPases and their associated regulatory proteins as targets for pharmaceutical intervention and in the involvement of these enzymes in human disease. (shrink)

This response briefly argues that post-phenomenology has always cut across the transcendental-empirical divide and is able to cultivate a deep respect for technologies in their otherness, without denying their relation to humanity. It does this by revisiting Don Ihde’s genetic phenomenological variations and tracing its relation to Gilbert Simondon’s ontogenesis. Having set up the historical nature of objects, the second part of this paper will take up Yoni Van Den Eede’s call for a more speculative approach.

One of the earliest structural changes observed in cells in response to many extracellular factors is membrane ruffling: the formation of motile cell surface protrusions containing a meshwork of newly polymerized actin filaments. It is becoming clear that actin reorganization is an integral part of early signal transduction pathways, and that many signalling molecules interact with the actin cytoskeleton. The small GTP‐binding protein Rac is a key regulator of membrane ruffling, and proteins that can regulate Rac activity, such as (...) Bcr, are likely to act on this signalling pathway. In addition, several previously characterized signal transducing molecules are implicated in the membrane‐ruffling response, including Ras, the adaptor protein Grb2, phosphatidyl inositol 3‐kinase, phospholipase A2 and phorbol ester‐responsive proteins. Changes in polyphosphoinositide metabolism and intracellular Ca2+ levels may also play a role. A number of actin‐binding and organizing proteins localize to membrane ruffles and are potential targets for these signal transducing molecules. (shrink)

This article discusses the concept of Biomimicry, which has been applying in many fields, from nanotechnology to robotics. It is appearing in smart materials and machinic intelligence, for diverse purposes, being inspired by natural processes and organisms. The main application of Biomimicry has been to produce artifacts and ideas from what we can know about what nature has already done. While the mimesis has been removed from the vocabulary of Art, the works of some artists are still full of possibilities (...) to discuss under the concept of Biomimetics. Many artists have dedicated themselves to the development of works using the poiesis of hybridization and mimicry. How close they approach of Biomimetics? As examples, are brought Walmor Corrêa, Patrícia Piccinini, Liu Xue, Berlinde De Bruyckere, Alessandro Boezio, Joan Fontcoberta and Pere Formiguera. This discussion is the starting point for introduce my project “VIRIDIUM”, in which I´m developing some semiautonomous and translucent robots, printed in 3D. The poetic basis is the possibility that nature has in hybridizing and evolving, spontaneously, as well as being hybridized by genetic manipulation. I propose the development of objects / beings that do not exist in the nature but refer and simulate behaviors of those who inhabit the world, in different kingdoms of Nature. I describe the first stage of the project, which focuses the Plantae kingdom. Afterwards of the Biomimicry and darwinian evolution concepts I bring the concept of Artification, as a possible model of understanding the poetic process, both in “VIRIDIUM” and in the works of the artists chosen. (shrink)

The molecular cloning of new neuroactive growth factors and their receptors has greatly enhanced our understanding of important interactions among receptors and singnaling molecules. These studies have begun to illuminate some of the mechanisms that allow for specificity in neuronal signaling. Model cell systems, such as the PC‐12 pheochromocytoma cell line, express receptors for these different neurotirophic factors, leading to comparisons of signaling pathways for these factors. Upon binding their ligands, these receptors undergo phosphorylation on tyrosine residues, which directs their (...) interaction with signaling proteins containing src homology (SH2) domains, sequences that mediate associations with tyrosine‐phosphorylated proteins. These SH2 proteins translate the tyrosine kinase activity of receptors into downstream events that result in the specific cellular response. Investigations such as these have revealed that molecular specificity in signaling pathways may arise from combinatorial diversity in interactions between receptors and key regulatory proteins. (shrink)

This article explores the rhythmic body with the example of the embodiment of the ‘bashment gal’ and the role she plays in the dancehall sound system session. It considers rhythm as an energetic patterning process operating both within and between media. Rhythm provides a means of communication and making sense that does not rely on representation or code. There are three elements to performance techniques of the rhythmic body – amplification, inflection and transduction. Amplification for the bashment gal’s performance (...) techniques involves increasing the size or effort of her dance movements, dancing in a chorus line accelerating her tempo. In what is considered as a hyper-sexualized arena of the dancehall session, it is argued that the bashment gal has to be understood in terms of African traditions where sexual pleasure and fertility are not separate. With rhythmic inflection the bashment gal gives distinctiveness to her performance, as is much prized in the style and fashion of the dancehall scene. The transduction of patterning from one medium to another, via tympanic surfaces, helps to forge the sound system session and the bashment gal as a rhythmic whole and fosters her sense of identity as a rhythmic body. (shrink)

Release of the ATP hydrolysis product ortophosphate (Pi) from the active site of myosin is central in chemo‐mechanical energy transduction and closely associated with the main force‐generating structural change, the power‐stroke. Despite intense investigations, the relative timing between Pi‐release and the power‐stroke remains poorly understood. This hampers in depth understanding of force production by myosin in health and disease and our understanding of myosin‐active drugs. Since the 1990s and up to today, models that incorporate the Pi‐release either distinctly before (...) or after the power‐stroke, in unbranched kinetic schemes, have dominated the literature. However, in recent years, alternative models have emerged to explain apparently contradictory findings. Here, we first compare and critically analyze three influential alternative models proposed previously. These are either characterized by a branched kinetic scheme or by partial uncoupling of Pi‐release and the power‐stroke. Finally, we suggest critical tests of the models aiming for a unified picture. (shrink)

Taste cells respond to a wide variety of chemical stimuli: certain ions are perceived as salty (Na+) or sour (H+); other small molecules are perceived as sweet (sugars) and bitter (alkaloids). Taste has evolutionary value allowing animals to respond positively (to sweet carhohydrates and salty NaCl) or aversively (to bitter poisons and corrosive acids). Recently, some of the proteins involved in taste transduction have been cloned. Several different G proteins have been identified and cloned from taste tissue: gustducin is (...) a taste cell specific G protein closely related to the transducins. Work is under way to clone additional components of the taste transduction pathways. The combination of electrophysiology, biochemistry and molecular biology is being used to characterize taste receptor cells and their sensory transduction mechanisms. (shrink)

For almost 30 years the ion channel that initiates the ON visual pathway in vertebrate vision has remained elusive. Recent findings now indicate that the pathway, which begins with unbinding of glutamate from the metabotropic glutamate receptor 6 (mGluR6), ends with the opening of the transient receptor potential (TRP)M1 cation channel. As a component of the mGluR6 signal transduction pathway, mutations in TRPM1 would be expected to cause congenital stationary night blindness (CSNB), and several such mutations have already been (...) identified in CSNB families. Furthermore, expression of TRPM1 in both the retina and skin raises the possibility that a genetic link exists between certain types of visual and skin disorders. (shrink)

Neuronal growth and remodelling are guided by both intracellular gene programs and extracellular stimuli. The growth cone is one site where the effects of these extrinsic and intrinsic factors converge upon the mechanical determinants of cell shape. We review the growth cone as a transduction device, converting extracellular signals into mechanical forces. A variety of soluble, extracellular matrix and membrane bound molecules control growth cone behavior. In addition, GAP‐43 is discussed as a possible component of the Intraneuronal gene program (...) which modulates growth cone activity. The GTP‐binding protein, Go, is a major growth cone membrane protein that may transduce signals not only from outside the cell, but from within as well. This may provide a molecular site in the growth cone for the coordination of a genetic growth program with environmental signals. (shrink)

Activation of resting T lymphocytes through the T cell antigen receptor complex is initiated by critical phosphorylation and dephosphorylation events that regulate the function and interaction of a number of signaling molecules. Key elements in these reactions are members of the Src, Syk and Csk families of protein tyrosine kinases (PTKs) and the phosphotyrosine phosphatases (PTPases) that regulate and/or counteract them, such as CD45. The PTKs can autophosphorylate and phosphorylate each other at multiple sites and, as the result of these (...) interactions, they are induced to phosphorylate other cellular proteins. These phosphorylation events lead to modulation of enzymatic activities and/or serve as binding sites for other signaling molecules having phosphotyrosine‐binding Src homology 2 (SH2) domains. As a result, these proteins translocate to the receptor complexes and are juxtaposed to the kinases that phosphorylate them. Some of the SH2‐domain‐containing polypeptides lack enzymatic activities and, instead, serve as adapter molecules that couple the signal to downstream effectors, such as regulators of the Ras proteins, and further into serine/threonine‐specific protein kinase cascades. Through largely unknown steps these reactions lead to the transcription of previously silent genes, activation of lymphocyte effector functions, progression through the cell cycle and cell proliferation. (shrink)

Cytoskeletal proteins provide the structural foundation that allows cells to exist in a highly organized manner. Recent evidence suggests that certain cytoskeletal proteins not only maintain structural integrity, but might also be associated with signal transduction and suppression of tumorigenesis. Since the time of the discovery of tensin, a fair amount of data has been gathered which supports the notion that tensin is one such protein possessing these characteristics. In this review, we discuss recent studies that: (1) elucidate a (...) role for tensin in maintenance of cellular structure and signal transduction; (2) implicate tensin as the anchor for actin filaments at the focal adhesion; (3) describe the phosphorylation of tensin; (4) describe potential targets for its Src homology region 2 domain; (5) describe the association between tensin and the nuclear protein p130; and (6) demonstrate that increased tensin expression in a cell line appears to reduce its transformation potential. (shrink)

Name der Zeitschrift: Semiotica Jahrgang: 2014 Heft: 202 Seiten: 673-688.