Biological Sciences
Signal Transduction Pathways
Signal transduction pathways are a series of molecular events that transmit signals from the cell surface to the nucleus, resulting in a specific cellular response. These pathways often involve the activation of receptors, intracellular signaling molecules, and ultimately the regulation of gene expression or other cellular processes. They play a crucial role in coordinating various cellular activities in response to external stimuli.
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12 Key excerpts on "Signal Transduction Pathways"
eBook - ePubBiochemistry
An Integrative Approach with Expanded Topics
- John T. Tansey(Author)
- 2022(Publication Date)
- Wiley(Publisher)
This chapter looks beyond regulation of enzymatic activity to examine some other facets of cell signaling, particularly in growth and dif ferentiation of cells and tissues. One of the advantages of specializing tissue function into storage (adipose), movement (muscle), and collected metabolic pathways (liver) is that an organism can have dedicated systems for these dif ferent metabolic roles. A complex organism needs to first generate these tissues and systems, then orchestrate their growth and dif ferentiation, and finally coordinate their response to dif ferent metabolic states. Collectively, all this information is significant not only in terms of basic biochemistry but also in immunology, developmental biology, and the processes involved in diseases such as cancer.21.1.1 Signal transduction follows certain basic principlesSignal transduction is generally accomplished through chemical signals, although some specialized cells can detect and respond to light. For communication to occur, three things need to be in place: a signal (a chemical compound released by other cells somewhere in the organism or by other organisms in the environment), a receptor for the signal, and a means by which the cell can respond (Figure 21.1 ). Signals are often hormones, and receptors are often transmembrane proteins.FIGURE 21.1 Fundamentals of signal transduction. In any signal transduction pathway, the binding of a signaling cell to a receptor initiates a cascade within the cell that ultimately results in alterations to enzyme activity or gene expression. Sometimes the signal is first propagated and amplified through a second messenger.The binding of the signal by the receptor on the extracellular side is specific, and it elicits a conformational change in the receptor that causes a change on the intracellular side of the protein. The change in the conformation typically activates enzymes such as kinases, and it can stimulate protein signaling pathways directly or be amplified by other enzymes and second messenger signaling molecules such as Ca2+ or cyclic AMP (cAMP). Recall that a second messenger
- Dhanjoo N. Ghista(Author)
- 2012(Publication Date)
- IntechOpen(Publisher)
Part 1 Biomedical Science: Disease Pathways, Models and Treatment Mechanisms 2 Cell Signalling and Pathways Explained in Relation to Music and Musicians John T. Hancock University of the West of England, Bristol, UK 1. Introduction Cell signalling is arguably the most important area of modern biology. The subject encompasses the control of cellular events, especially in response to extracellular factors. It has been suggested that the human body is one of the most complex machines ever produced (Dawkins, 1989) and the regulation of the activities within it are also equally complex. Interest in cell signalling does not simply stem from an academic viewpoint either. Certainly there is a vast resource of research which is focuses on the investigation of signalling pathways and the control which they bestow on a cell. However, there are tangible reasons to take an interest here too. The vast majority of new pharmaceutical compounds under development are aimed at the modulation of proteins involved in cell signalling events (Filmore, 2004). Such proteins may be G protein-coupled receptors (GPCRs) or perhaps kinases which are downstream of such receptors. Many anti-cancer studies are now focused on the development of compounds which modulate Mitogen Activated Protein Kinases (MAPKs) for example. Therefore, an understanding the working of the components of a signal transduction opens up avenues for the future modulation of such activities with the development of new therapies and pharmaceutical agents. The study of cell signalling can seem very daunting. Vast diagrams full of acronyms can put off the most ardent reader, but there are many basic principles which underpin the subject. In cell signalling compounds are made and initiate a response, and this is true whether the molecule originates outside the cell or is created inside.
eBook - ePubBipolar Disorder
Clinical and Neurobiological Foundations
- Lakshmi N. Yatham, Mario Maj, Lakshmi N. Yatham, Mario Maj(Authors)
- 2011(Publication Date)
- Wiley(Publisher)
Over the past 10 years, studies using animal models, postmortem brain tissue and lymphocytes samples have examined the intracellular Signal Transduction Pathways linked to neurotransmitters to investigate the biological basis of BD. In this chapter, we will review the evidences for abnormalities in Signal Transduction Pathways in BD. We will also discuss how these pathways may be relevant in the treatment of this illness with mood stabilizing medication.Signal Transduction PathwaysSignal Transduction Pathways are uniquely responsible for coordinating the cellular response to information impinging on the cell from multiple sources and time frames [17]. These pathways follow a broadly similar course that can be viewed as a molecular circuit, which can detect, amplify and integrate diverse external signals to generate cellular response such as enzyme activity, stimulation of proliferation or cell death and lastly induced gene expression [17].Abnormalities in these pathways may lead to a functional imbalance in multiple neurotransmitter pathways, which could account for the diverse clinical features found in BD [18]. Most neurotransmitter receptors are coupled to guanine-nucleotide binding proteins (G-protein). These proteins link receptors to specific enzymes that activate second messengers, or alternatively, they link to specific ion channels. Now, the extracellular signals are integrated, amplified and transmitted to specific intracellular enzymes, called effectors, which catalyse the production of an extensive array of cascading second messengers. In turn, these messenger molecules act on various protein kinases [17]. The activation of these kinases is instrumental in regulating diverse intracellular processes, including gene expression, and in relating these to lasting neurobiological changes [17].The number of findings for abnormalities in signal transduction systems in samples obtained directly from patients is growing. Indeed, animal and cell culture studies have demonstrated pharmacological effects of mood stabilizers, especially lithium, suggesting its role in neuroprotection, which range from reducing excitotoxicity through increased glutamate uptake, to regulation of a number of second messenger systems, such as adenylate cyclase (cyclic adenosine monophosphate, cAMP), phosphoinosi-tide (PI), protein kinase C (PKC), protein kinase A (PKA), protein kinase B (AKT) and glycogen synthase kinase-3 (GSK-3) [19].
eBook - ePubAdvanced Molecular Biology
A Concise Reference
- Richard Twyman(Author)
- 2018(Publication Date)
- Garland Science(Publisher)
diverge, allowing multiple stimuli to generate similar responses, and individual signals to effect different responses. Further diversity is generated by different responses to the length and intensity of the stimulus, and the cell-specific synthesis of different receptors and signaling components. Signal Transduction Pathways are subject to complex regulatory networks, and the response depends upon a balance of opposing forces in the cell.- Delivery of the signal involves the activation or repression of transcription factors, enzymes and structural components of the cell, usually by altering their state of phosphorylation.
28.1 Receptors and signaling pathways
Cell-surface receptors and their ligands. Cells respond to a diverse range of signals through an equally diverse range of receptors. In metazoans, many signals are small polypeptides. Locally acting (paracrine) polypeptide signals are termed growth factors (or cytokines in the hematopoietic system) and can be assigned to families according to structural or functional similarities. These molecules are concerned not only with cell growth, but also with differentiation, motility and other cellular functions. Hormones are endocrine signaling molecules and many are peptides like growth factors, but there are also large glycoprotein hormones and steroid hormones, the latter able to diffuse directly through the plasma membrane of the cell and interact with cytoplasmic and nuclear receptors. Another important class of peptide signaling molecules is the neuropeptides, which mediate neurotransmission and neuromodulation in the central and peripheral nervous systems. Cells can also respond to numerous small molecules such as amino acids, nucleotides and bioactive amines, as well as macromolecules embedded in the extracellular matrix or displayed on the surface of adjacent cells, which control cell motility and adhesion. Some receptors bind contra-receptors
eBook - PDF- Gerald Karp, Janet Iwasa, Wallace Marshall(Authors)
- 2018(Publication Date)
- Wiley(Publisher)
● Signals from the same ligand, such as EGF or insulin, can diverge to activate a variety of different effectors and path- ways, leading to diverse cellular responses. ● Signals can be passed back and forth between different pathways, a phenomenon known as cross‐talk. These characteristics of cell‐signaling pathways are illustrated schematically in FIGURE 15.33. Signaling pathways provide a mechanism for routing infor- mation through a cell, not unlike the way the central nervous sys- tem routes information to and from the various organs of the body. Just as the central nervous system collects information about the environment from various sense organs, the cell receives information about its environment through the activation of vari- ous surface receptors, which act like sensors to detect extracellular stimuli. Like sense organs that are sensitive to specific forms of stimuli (e.g., light, pressure, or sound waves), cell‐surface recep- tors can bind only to specific ligands and are unaffected by the presence of a large variety of unrelated molecules. A single cell may have dozens of different receptors sending signals to the cell interior simultaneously. Once they have been transmitted into the cell, signals from these receptors can be selectively routed along a number of different signaling pathways that may cause a cell to divide, change shape, activate a particular metabolic pathway, or even commit suicide (discussed in a following section). In this way, the cell integrates information arriving from different sources and mounts an appropriate and comprehensive response. Different signaling pathways are often interconnected. As a result, signals from a variety of unrelated ligands can converge to FIGURE 15.32 A simplified model of the role of Ca 2+ in guard cell closure. (a) Photograph of stomatal pores, each flanked by a pair of guard cells.
eBook - ePubCellular Signal Transduction in Toxicology and Pharmacology
Data Collection, Analysis, and Interpretation
- Jonathan W. Boyd, Richard R. Neubig, Jonathan W. Boyd, Richard R. Neubig(Authors)
- 2019(Publication Date)
- Wiley(Publisher)
9 Future Research in SignalingJonathan W. Boyd1 Department of Orthopaedics and Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV, USA2 Department of Orthopaedics, West Virginia University School of Medicine, Morgantown, WV, USA3 Department of Oecotrophologie, Fulda University of Applied Sciences, Fulda, Hesse, Germany1, Nicole Prince2, and Marc Birringer3The aim of this book is to inform the reader about the intimate relationship between signal transduction and cellular survival/death, but the overarching goal of all mechanistic toxicology and pharmacology is to better understand both the causes of disease and potential treatments. With this goal in mind, it is important to identify areas of future research that could improve our understanding of cell signaling and serve as a bridge that better connects cellular response with disease states. There are some interesting recent studies that provide unique perspectives on signal transduction, which we hope will provide both insight and inspiration to further enhance our understanding of the integration of cellular signaling networks into tissues, organs, and whole organisms.9.1 Translational Research and a Spatiotemporal Understanding of Signal Transduction
For cellular signal transduction research to reach its potential in toxicology and pharmacology, it is necessary to bridge the gap between early responses and end disease states. Individual cells are preprogrammed with a certain amount of robustness that allows them to respond to many different types of exposures and conditions, but in a eukaryotic organism, they also possess the ability to sense and respond to a multicellular environment. Signaling responses to changes in the localized environment can lead to critical cellular bifurcations, which may result in altered processes or functions for the individual cell. The modified functions of this single cell may impact other local cells, which changes their
No longer available |Learn more- David Latchman(Author)
- 2020(Publication Date)
- Garland Science(Publisher)
Figure 8.4 ). The mechanisms by which cellular signaling pathways regulate transcription factor activity are considered in this chapter.FIGURE 8.3 The post-translational activation of transcription factor A (a) allows a much more rapid response than the de novo transcription of the gene encoding transcription factor B (b), which requires multiple stages before transcription factor protein is produced.FIGURE 8.4 Production of a biological effect by a specific signal can occur by the signal activating a transcription factor. The transcription factor then activates its target genes, resulting in enhanced levels of the proteins they encode, thereby producing the appropriate change in cellular phenotype.Multiple mechanisms regulate transcription factor activity
As indicated in Figure 8.5 , a number of different mechanisms allow the regulation of transcription factor activity. In the case of signaling molecules that can enter the cell, direct binding of the ligand to the transcription factor is a frequently used mechanism for transcription factor activation. The regulation of transcription factors by such intracellular ligands is therefore discussed in Section 8.1 (Figure 8.5a ). Conversely, signaling molecules that bind to cell surface receptors and cannot enter the cell frequently act by inducing enzymes that can post-translationally modify proteins, for example, by phosphorylation (Figure 8.5b ). The post-translational modification of transcription factors by phosphorylation is therefore discussed in Section 8.2 and other post-translational modifications that regulate transcription factor activity are discussed in Section 8.3
- David Van Vranken, Gregory A. Weiss, GREGORY A WEISS(Authors)
- 2018(Publication Date)
- Garland Science(Publisher)
We have come full circle. We started this book by describing how the transcription of genes leads to all of the downstream biooligomers in the human cell. Filling in the details took up most of the book. With this chapter we have concluded our journey by describing how small molecules and macromolecules, ultimately produced by bio-oligomers, can control the transcription of other biooligomers in the cell. Moreover, we covered many examples where synthetic small molecules could be used to control signal transduction processes, many of which involve transcription. Biooligomers are an architectural paradigm for the efficient generation of molecular diversity—an essential ingredient in the recipe for evolution. You are now empowered to understand and control biology at the highest level of relevant detail—the level of atoms and bonds. At the level of atoms and bonds you can engineer the medicines of the future or probe the secrets of cells that make us healthy, unhealthy, and human.LEARNING OUTCOMES- Interpret the boolean logic of signal transduction diagrams as it applies to control of gene expression.
- Predict the effects of inhibitors and activators on Signal Transduction Pathways.
- Understand the connection between Ca2+ ions and two rapid nontranscriptional processes: muscle contraction and exocytosis.
- Distinguish the seven major Signal Transduction Pathways that control transcription in human cells.
- Recognize the high-affinity ligands for nuclear receptors.
- Know the three types of ligands for human two-component pathways: interleukins, interferons, and TGF-β.
- Recognize growth factors as the ligands for receptor tyrosine kinases.
- Distinguish between the four subpathways downstream of receptor tyrosine kinases: STAT, MAP kinases, PLCγ, and PI3K/Akt.
- Distinguish the death pathways (TNFα and FADD) from receptor tyrosine kinase pathways.
- Recognize the common classes of ligands that act at GPCRs.
- Distinguish between adenylyl cyclase and PLCβ pathways controlled by 7TM GPCRs.
- Recognize the imbalance between K+ , Na+ , and Ca2+ ions in human cells.
- Understand how proteolytic degradation is modulated through signaling.
- Recognize the two diffusible gases that are important in human cell signaling: NO and O2
eBook - PDF- Shirley Lehnert(Author)
- 2007(Publication Date)
- CRC Press(Publisher)
11 Modulation of Radiation Response via Signal Transduction Pathways 11.1 Intracellular Signaling Exposure of cells to stress activates multiple intracellular signaling or Signal Transduction Pathways along which signals move from the outside of the cell to the inside and between different intracellular locations. The result is an alteration in cellular activity and changes in the program of genes expressed in the responding cells. Ionizing radiation is one of the stresses that can initiate intracellular signaling and the response to that signaling can in turn modulate radiation response. In this chapter, the key players in the signal transduction process are briefly described and the dual effects of radiation-induced signaling and signal-mediated modulation of radiation response are discussed. Much of the material in this chapter is based on reviews by Schmidt-Ullrich et al. [1], Dent et al. [2], and the references listed therein. 11.2 Transmembrane Receptors Signaling is initiated by cytokines, low molecular weight hormones, growth factors, and other proteins that arrive at the plasma membrane and precipi-tate intracellular events by interacting with cell surface receptors that span the plasma membrane. The outer (extracellular) domain of these receptors is activated by selectively binding a receptor-specific protein or ligand and signals are transferred to the intracellular domain, setting off an intracellu-lar signal transduction cascade. In the case of growth factor (GF) receptors, transmembrane signal trans-duction is initiated at the outer surface of the cell membrane by the binding of a GF to the extracellular domain of its cognate receptor. Outside the cell, GF receptor proteins have a ligand binding N-terminal ectodomain, fol-lowed by a membrane-spanning transmembrane domain. At their C-termini 251
eBook - PDFKarp's Cell and Molecular Biology
Concepts and Experiments
- Gerald Karp, Janet Iwasa, Wallace Marshall(Authors)
- 2016(Publication Date)
- Wiley(Publisher)
A quick look at Figure 15.15 or 15.25 b, c illustrates how a single stimulus—a ligand binding to a GPCR or an insulin receptor—sends signals out along a variety of different pathways. 3. Cross‐talk. In previous sections, we examined a number of sign- aling pathways as if each operated as an independent, linear chain of events. In fact, the information circuits that operate in cells are more likely to resemble an interconnected web in which components produced in one pathway can participate in events occurring in other pathways. The more that is learned about information signaling in cells, the more cross‐talk between sign- aling pathways that is discovered. Rather than attempting to cata- log the ways that information can be passed back and forth within a cell, we will look at an example involving cAMP that illustrates the importance of this type of cross‐talk. Cyclic AMP was depicted earlier as an initiator of a reaction cascade leading to glucose mobilization. However, cAMP can also inhibit the growth of a variety of cells, including fibroblasts and fat cells, by blocking signals transmitted through the MAP kinase cas- cade. Cyclic AMP is thought to accomplish this by activating PKA, the cAMP‐dependent kinase, which can phosphorylate and inhibit Ras PIP 2 PDGF, EGF, etc. Tyrosine kinase-linked receptors G Protein-coupled receptors IP 3 Ca 2+ IP 3 R DAG PLCβ PLCγ Cellular activity & mitogenesis R Acetylcholine, histamine NA, 5-HT, ATP, PAF, TXA2, Glutamate, Angiotensin II, Vasopressin, Bradykinin, Substance P, Bombesin, Neuropeptide Y, Thrombin, Cholecystokinin, Endothelin, Neuromedin, TRH, GnRH, PTH Odorants, Light I II III P P PKC PI3K PIP 3 Raf MAP kinase GAP G FIGURE 15.33 Examples of convergence, divergence, and cross‐talk among various signal‐transduction pathways. This drawing shows the outlines of signal‐transduction pathways initiated by receptors that act by means of both heterotrimeric G proteins and receptor protein‐tyrosine kinases.
eBook - ePubFrom Molecules to Networks
An Introduction to Cellular and Molecular Neuroscience
- Ruth Heidelberger, M. Neal Waxham, John H. Byrne, James L. Roberts(Authors)
- 2009(Publication Date)
- Academic Press(Publisher)
Therefore, predictions of behavior that neglect fluctuations may be false. Nevertheless, for many biochemical pathways, continuous models consisting of sets of differential equations (e.g., Eqs. 14.12 – 14.15) will remain essential because of insufficient data to justify a stochastic model. Generally, data used to construct a continuous model relies on large and reproducible changes in pathway fluxes and concentrations following strong stimuli. Because those responses are reproducible, a continuous model may be expected to reliably predict responses to new stimuli of similar strength to those used in model construction. Genes can be Organized into Networks that are Activated by Signaling Pathways Gene regulation is a common end point of biochemical signaling pathways. As discussed in Chapter 13, signaling pathways often activate proteins termed transcription factors (TFs) (Kewley et al., 2004). Activation is often via phosphorylation of critical amino acid residues. Activated TFs regulate the transcription of genes by binding to nearby short segments of DNA. In Chapter 13, these segments were referred to as cis -regulatory elements. Another term is response elements. If these elements activate transcription, they are commonly termed enhancers ; if they repress transcription, they are commonly termed silencers. Many genes are regulated by multiple TFs. Genes coding for TFs can be repressed or activated by TFs, including their own products. Large clusters of genes are often regulated in concert by biochemical signaling pathways that activate specific TFs. For example, activation of MAPK can lead to activation of hundreds of genes and repression of many others (Roberts et al., 2000). Gene networks may be defined as gene clusters in which the expression of some members is regulated by the protein products of other members, or by a common input such as a hormone or neurotransmitter stimulus. The expression of network genes varies in a coordinated manner
- Alfredo Meneses(Author)
- 2013(Publication Date)
- Elsevier(Publisher)
8Basic Elements of Signal Transduction Pathways Involved in Chemical Neurotransmission
Claudia González-Espinosa and Fabiola Guzmán-Mejía, Pharmacobiology Department, Center for Research and Advanced Studies (Cinvestav), South Campus, Mexico City, MéxicoDistinct process of signal transduction triggered in neurons by receptors to neurotransmitters and neuromodulators have been recognized as responsible for long-term changes on synapse function. Some of those biochemical modifications to the metabolism of information inside neurons are thought related to memory formation and consolidation. Basic notions of signal transduction are, then, necessary for the understanding of current literature and hypothesis on the neurotransmitter systems involved in prolonged alterations to neuronal function. This chapter briefly summarizes some fundamental concepts and elements of the signal transduction systems involved in synaptic chemical transmission.Keywords
Signal transduction; chemical neurotransmission; G-protein-coupled receptors.Introduction
Research on cellular and molecular mechanisms involved in learning and memory constitutes a leading area in neuroscience that started long time ago. Since the mid-twentieth century, researchers have been concerned not only in finding the neurotransmitter systems involved in the transmission of electrical stimuli between nerve cells, but also in determining the long-term molecular changes that lead to long-term modifications to neural activity due to the neurotransmission process. One of the underlying hypothesis of molecular approaches to neurotransmission is that specific characteristics on the neuron-to-neuron communication (such as the intensity, duration, and composition of the signal) induce particular and sometimes irreversible modifications on neuron physiology leading to learning and memory consolidation. Description of the main neurotransmitter systems came together with the discovery of important changes in the postsynaptic terminals after the learning process. Those findings contributed to the late recognition of the importance of signal transduction events on the generation and maintenance of long-term changes on neural function, and allowed researchers to propose that abnormalities on particular signaling cascades could lead to modifications on the learning and memory processes.
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