Signal Transduction

10 Key excerpts on "Signal Transduction"

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  eBook - PDF

  Color Atlas of Biochemistry

  • Jan Koolman, Klaus-Heinrich Röhm(Authors)
  • 2012(Publication Date)
  • Thieme

    (Publisher)

  Signaling Systems Signa l Transduc tion Signal Transduction 398 Signal Transduction For a multicellular organism to be capable of life, its cells must be able to communicate with one another. This is achieved mainly with the assistance of extracellular signaling molecules , which can act over great or short distances by binding to receptors . Most cells are able both to send out and to receive signals. The mechanisms of Signal Transduction in or-ganisms follow shared principles and the in-volved molecules form families that have a degree of kinship. The principles of intracellu-lar signaling were obviously established early in the course of evolution. A. Signal Transduction There are hundreds of different signals that can affect cellular activity and they can be very different in nature. Hormones , neurotransmit-ters , mediators , odorants , flavors , metabolites , and membrane components of other cells are chemical signals . Specialized cells can also per-ceive physical signals , e.g., light , electrical im-pulses , or mechanical stimuli . Perception of light, for example, enables animals to see (p. 368). Mechanoreception is involved in hearing and pressure regulation. Ion channels that react to action potentials (p. 360) are re-ceptors for electrical impulses. The great majority of signaling substances are hydrophilic molecules . They bind to receptor proteins (p. 400) on the plasma membrane of their target cells. This activates a signal path-way in which various intracellular signaling proteins take part. These ultimately regulate the activity of effector proteins , thereby alter-ing the behavior of the cell. Effector proteins can be transcription factors, metabolic en-zymes, components of the cytoskeleton , or ion channels . While regulation of the cells by alter-ing their gene expression takes hours to be-come effective, the adjustment of metabolism and the control of motions and ion concentra-tions proceed much faster (in seconds to min-utes).

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  Computational Systems Biology

  From Molecular Mechanisms to Disease

  • Andres Kriete, Roland Eils(Authors)
  • 2013(Publication Date)
  • Academic Press

    (Publisher)

  Chapter 4

  Biological Foundations of Signal Transduction, Systems Biology and Aberrations in Disease

  Ursula Klingmüller, Marcel Schilling, Sofia Depner and Lorenza A. D’Alessandro,    Division Systems Biology of Signal Transduction, German Cancer Research Center (DKFZ), Heidelberg, Germany ,    

  E-mail: [email protected]

  Abstract

  Cellular communication is mediated by extracellular stimuli that bind cellular receptors and activate intracellular signaling pathways. Principal biochemical reactions used for Signal Transduction are protein or lipid phosphorylation, proteolytic cleavage, protein degradation and complex formation mediated by protein-protein interactions. Within the nucleus, signaling pathways regulate transcription factor activity and gene expression. Cells differ in their competence to respond to extracellular stimuli. A deeper understanding of complex biological responses cannot be achieved by traditional approaches but requires the combination of experimental data with mathematical modeling. Following a systems biology approach, data-based mathematical models describing sub-modules of signaling pathways have been established. By combining computer simulations with experimental verification systems properties of signaling pathway including cycling behavior or threshold response could be identified. Yet, to analyze complex growth and maturation processes at a systems level and quantitatively predict the outcome of perturbations further advances in experimental and theoretical methodologies are required.

  Keywords

  Signaling; Protein; Modeling; Dynamic; Parameter; Multiplex analysis

  1 Introduction

  Cells do not live in isolation, but have evolved mechanisms to communicate. Principal signals used are direct cell-cell contact and secreted molecules that bind to cell surface receptors. Arrays of intracellular proteins form Signal Transduction pathways and connect to receptors. This facilitates signal transmission from the extracellular compartment to the nucleus and thereby triggering various biological responses. A key mechanism used for Signal Transduction is phosphorylation due to its simplicity, flexibility, and reversibility. In the late 1970s it was discovered that the oncogene v-Src can transform cells, possesses protein kinase activity and causes an increase in tyrosine phosphorylation (Hunter and Sefton 1980

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  Cell Signaling

  • (Author)
  • 2014(Publication Date)
  • Research World

    (Publisher)

  ________________________ WORLD TECHNOLOGIES ________________________ Chapter- 6 Signal Transduction Overview of Signal Transduction pathways Signal Transduction comes from the verb to 'transduce' meaning to 'lead across'. In biology Signal Transduction is the process by which an extracellular signaling molecule activates a membrane receptor that in turn alters intracellular molecules to create a response. Transmembrane receptors span the cell membrane, with part of the receptor outside and part inside the cell. The chemical signal binds to the outer portion of the receptor, changing its shape and conveying another signal inside the cell. Some chemical ________________________ WORLD TECHNOLOGIES ________________________ messengers, such as testosterone, can pass through the cell membrane, and bind directly to receptors in the cytoplasm or nucleus. Sometimes there is a cascade of signals within the cell. With each step of the cascade, the signal can be amplified, so a small signal can result in a large response. Eventually, the signal creates a change in the cell, either in the expression of the DNA in the nucleus or in the activity of enzymes in the cytoplasm. These processes can take milliseconds (for ion flux), minutes (for protein- and lipid-mediated kinase cascades), hours, or days (for gene expression). Signaling molecules Most Signal Transduction involves the binding of extracellular signaling molecules (and ligands) to cell-surface receptors. While triggering events inside the cell, such receptors typically face outward from the plasma membrane. Intracellular signaling cascades can also be triggered through cell-substratum interactions. One example is integrins, which bind ligands found within the extracellular matrix. Steroids are another example of extracellular signaling molecules that may cross the plasma membrane due to their lipophilic or hydrophobic nature.

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  Cell Signaling and Imaging

  • (Author)
  • 2014(Publication Date)
  • Academic Studio

    (Publisher)

  ________________________ WORLD TECHNOLOGIES ________________________ Chapter 6 Signal Transduction Overview of Signal Transduction pathways Signal Transduction comes from the verb to 'transduce' meaning to 'lead across'. In biology Signal Transduction is the process by which an extracellular signaling molecule activates a membrane receptor that in turn alters intracellular molecules to create a response. Transmembrane receptors span the cell membrane, with part of the receptor outside and part inside the cell. The chemical signal binds to the outer portion of the receptor, changing its shape and conveying another signal inside the cell. Some chemical ________________________ WORLD TECHNOLOGIES ________________________ messengers, such as testosterone, can pass through the cell membrane, and bind directly to receptors in the cytoplasm or nucleus. Sometimes there is a cascade of signals within the cell. With each step of the cascade, the signal can be amplified, so a small signal can result in a large response. Eventually, the signal creates a change in the cell, either in the expression of the DNA in the nucleus or in the activity of enzymes in the cytoplasm. These processes can take milliseconds (for ion flux), minutes (for protein- and lipid-mediated kinase cascades), hours, or days (for gene expression). Signaling molecules Most Signal Transduction involves the binding of extracellular signaling molecules (and ligands) to cell-surface receptors. While triggering events inside the cell, such receptors typically face outward from the plasma membrane. Intracellular signaling cascades can also be triggered through cell-substratum interactions. One example is integrins, which bind ligands found within the extracellular matrix. Steroids are another example of extracellular signaling molecules that may cross the plasma membrane due to their lipophilic or hydrophobic nature.

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  eBook - ePub

  Advanced Molecular Biology

  A Concise Reference

  • Richard Twyman(Author)
  • 2018(Publication Date)
  • Garland Science

    (Publisher)

  Chapter 28

  Signal Transduction

  Fundamental concepts and definitions

  • Cells respond to their environment by reorganizing their structure, regulating the activity of proteins and altering patterns of gene expression. The stimulus for such responses is termed a signal, and may be a small molecule, a macromolecule or a physical agent, such as light. Signals interact with the responding cell through molecules termed receptors.
  • Small molecules often act as diffusible signals. In unicellular organisms, diffusible signals may be environmental in origin or may be released from other cells (e.g. yeast mating-type pheromones, cAMP in Dictyostelium). In metazoans, signals may be released from nearby cells and diffuse over short distances (paracrine signaling), or they may be released from distant cells and reach their target through the vascular system (endocrine signaling). Macromolecular signals are often associated with the extracellular matrix or displayed on the surface of neighboring cells (juxtacrine signaling). A molecular signal that binds to a receptor is termed a ligand.
  • Signals may be processed in three ways. Certain chemical signals may penetrate the plasma membrane of the cell and interact with internal receptors (e.g. steroids, nitric oxide). Most signals, however, are hydrophilic molecules remaining outside the cell. These interact with transmembrane (membrane-spanning) or membrane-associated receptors and cause a change of receptor structure. The interaction may result in signal transport, i.e. the signaling molecule is internalized (either by carriage caused by the conformation change of the receptor, by the creation of a pore, e.g. in the case of ion channels, or by receptor-mediated endocytosis). Alternatively, the conformational change in the receptor may induce enzyme activity inside the cell which mediates downstream effects while the ligand remains on the outside (Signal Transduction). Physical stimuli may also interact with receptors or may mediate their effects directly. Light stimulates the G-proteins linked to rhodopsin and cone opsin receptors when photons cause a conjugated light-sensitive molecule 11-cis retinal to change to the all-trans

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  Signal Transduction

  • Bastien D. Gomperts, ljsbrand M. Kramer, Peter E.R. Tatham(Authors)
  • 2002(Publication Date)
  • Academic Press

    (Publisher)

  i Prologue: Signal Transduction, origins and personalities m Transduction, the word and its meaning: one dictionary, different points of view The expression Signal Transduction first made its mark in the biological lit- erature around 1974, ~ and as a title word in 1979. 2-4 Physical scientists and electronic engineers had earlier used the term to describe the conversion of energy or information from one form into another. For example, a micro- phone transduces sound waves into electrical signals. Its widespread use in biospeak was triggered by an important review by Martin Rodbell, pub- lished in 1980 (Figure 1.1). 5 He was the first to draw attention to the role of IIII II IIIII I Alfred G Gilman and Martin Rodbell, awarded the Nobel Prize, 1994for their discovery of G-proteins and the role of these proteins in Signal Transduction in cells Figure I. I Occurrence of the term Signal Transduction. The left-hand axis records all papers using this term traced through the MedLine database.The right-hand axis records the proportion of papers using the term cell that also use the term Signal Transduction. 9 t(i> . . . . . . . . . GTP and GTP-binding proteins in metabolic regulation and he deliberately borrowed the term to describe their role. Bythe year 2000, 12% of all papers using the term cell also employed the expression Signal Transduction. I Hormones, evolution and history These chemical messengers.., or'hormones' (from 6p~um, meaning I excite or I arouse), as we may call them, have to be carried from the organ where they ate produced to the organ which they affect, by means of the bloodstream, and the continually recurring physiological needs of the organism must deter- mine their repeated production and circulation throughout the body.

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  Pharmacology

  Principles and Practice

  • Miles Hacker, William S. Messer, Kenneth A. Bachmann(Authors)
  • 2009(Publication Date)
  • Academic Press

    (Publisher)

  Chapter 6. Signal Transduction and Second Messengers

  Karen Lounsbury

  Outline

  6.1 Receptor Communication 103

  6.1.1 Ion Channels 103

  6.1.2 G-Protein Coupled Receptors 103

  6.1.3 Receptor Tyrosine Kinases 107

  6.1.4 Cytokine Receptors (Tyrosine Kinase-Associated Receptors) 109

  6.1.5 Intracellular Receptors 109

  6.1.6 Other Classes of Receptors 110

  6.2 Receptor/Second Messenger Crosstalk 110

  6.3 Signal Transduction Targets for Drug Discovery 111

  Central to the communication between cells is the process of Signal Transduction. Signal Transduction is the mechanism by which cell surface receptors receive information from extracellular signals such as hormones and neurotransmitters, and amplify this information through the actions of second messengers. Second messengers in turn activate pathways intrinsic to processes such as protein secretion, cell differentiation, and cell division. Many pharmacological agents elicit their clinical activity and side effects through interactions with receptors and/or their downstream signaling targets. As our understanding of receptor signaling has progressed, intracellular signaling molecules have become a major target of drug discovery. This chapter will review the major receptor-mediated signaling pathways and will outline current and future therapeutic strategies to target these pathways.

  6.1. Receptor Communication

  Receptors are the primary sensors of the cell environment, but ligand binding alone is useless without Signal Transduction. The effect of a pharmacologic agent on the ability of receptors to couple to downstream signals thus defines whether it will increase (agonist) or decrease (antagonist) the physiologic activity of the receptor. Selective regulation of the magnitude, time-course, and spread of the signal allows a single ligand to transmit a complex set of physiological effects. Signal Transduction by receptors can be broken into four major categories:

  ▪ Ion channels ▪ G protein-coupled receptors ▪ Receptor tyrosine kinases ▪ Intracellular receptors

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  Karp's Cell Biology

  • Gerald Karp, Janet Iwasa, Wallace Marshall(Authors)
  • 2018(Publication Date)
  • Wiley

    (Publisher)

  Virtually every activity in which a cell is engaged is regulated by signals originating at the cell surface. This overall process in which information carried by extracellular messenger molecules is translated into changes that occur inside a cell is referred to as Signal Transduction. Finally, signaling has to be terminated. This is important because cells have to be responsive to additional messages that they may receive. The first order of business is to eliminate the extracellular messenger molecule. To do this, certain cells Active Inactive Protein kinase 2 P Protein kinase 2 Active Protein kinase 1 Active Protein kinase 3 Inactive Protein kinase 3 P Active Transcription factor Inactive Transcription factor P DNA mRNA P FIGURE 15.3 Signal Transduction pathway consisting of protein kinases and protein phosphatases whose catalytic actions change the conformations, and thus the activities, of the proteins they modify. In the example depicted here, protein kinase 2 is activated by protein kinase 1. Once activated, protein kinase 2 phosphorylates protein kinase 3, activating the enzyme. Protein kinase 3 then phospho- rylates a transcription factor, increasing its affinity for a site on the DNA. Binding of a transcription factor to the DNA affects the transcription of the gene in question. Each of these activation steps in the pathway is reversed by a phosphatase. 628 CHAPTER 15 • Cell Signaling Pathways FIGURE 15.4 A comparison in the frequency of tyrosine phosphorylation in two different types of breast cancer cells. The panels on the left side of the figure show the frequency of phosphoty- rosine (pTyr) residues in certain proteins (named on the right side of the figure) in triple‐negative breast cancer cell lines. Triple‐negative cells do not express three major molecular signatures of many breast cancer cells–estrogen receptor, progesterone receptor, and the growth factor receptor HER2.

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  Biochemistry of Vision

  • Hitoshi Shichi(Author)
  • 2012(Publication Date)
  • Academic Press

    (Publisher)

  In the direct mechanism, a signal compound enters the cell and evokes cellular responses. the indirect mechanism. Light binds to specific photosensitive molecules (photoreceptors) and induces changes in concentrations of second messen-gers that, in turn, modulate membrane permeabilities to ions. Thus, light acts like a hormone that exerts its effect indirectly. It is for this reason that this chapter is included here and the current status of our knowledge of various systems of indirect signal transmission is reviewed. Information processing by the indirect mechanism occurs through at least five discrete steps (Table I) (2): (1) reception of the external substance by the specific receptor located on the external surface of the plasma membrane; (2) transfer of the signal, but not the substance itself, across the membrane; TABLE I Steps Involved in Information Transfer from Extracellular Substance to Intracellular Response Unit 1. Reception and recognition of external signal 2. Transmembrane transfer of signal 3. Transmission of signal from membrane to intracellular messenger 4. Eliciting responses 5. Termination I. General Mechanisms of Signal Transmission 207 (3) transmission of the signal from the internal surface of the membrane to an intracellular (second) messenger; (4) eliciting of cellular responses by the second messenger; (5) termination of the response and restoration of the initial state. Cellular responses to the external signals vary considerably depending on the type of signal and the function of cell that receives it. In spite of the diversities in responses, various receptor cells do show common features in their mechanism of signal transmission. For example, binding of a variety of hormones (e.g., catecholamines and glucagon) to the respective receptors results in the activation of adenylate cyclase, which synthesizes cyclic AMP as a second messenger within the cell.

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  Karp's Cell and Molecular Biology

  Concepts and Experiments

  • Gerald Karp, Janet Iwasa, Wallace Marshall(Authors)
  • 2016(Publication Date)
  • Wiley

    (Publisher)

  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 activate a common effector, such as Ras; signals from the same ligand can diverge to activate a variety of different effectors; and sig- nals can be passed back and forth between different pathways (cross‐ talk). The following are examples of these types of interactions. 1. Convergence. We have discussed two distinct types of cell‐surface receptors in this chapter: G protein‐coupled receptors and recep- tor tyrosine kinases. Another type of cell‐surface receptor that is capable of Signal Transduction was discussed in Chapter 7, namely, integrins. Although these three types of receptors may bind to very different ligands, all of them can lead to the forma- tion of phosphotyrosine docking sites for the SH2 domain of the adaptor protein Grb2 in close proximity to the plasma membrane (FIGURE 15.34). The recruitment of the Grb2‐Sos complex results in the activation of Ras and transmission of signals down the MAP kinase pathway. As a result of this convergence, signals from diverse receptors can lead to the transcription and translation of a similar set of growth‐promoting genes in each target cell. 2. Divergence. Evidence of signal divergence has been evident in virtually all of the examples of Signal Transduction that have been described in this chapter. 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.

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