Autocrine Signaling

8 Key excerpts on "Autocrine Signaling"

• 

  eBook - PDF

  Biology 2e

  • Mary Ann Clark, Jung Choi, Matthew Douglas(Authors)
  • 2018(Publication Date)
  • Openstax

    (Publisher)

  Because of their form of transport, hormones become diluted and are present in low concentrations when they act on their target cells. This is different from paracrine signaling, in which local concentrations of ligands can be very high. Autocrine Signaling Autocrine signals are produced by signaling cells that can also bind to the ligand that is released. This means the signaling cell and the target cell can be the same or a similar cell (the prefix auto- means self, a reminder that the signaling cell sends a signal to itself). This type of signaling often occurs during the early development of an organism to ensure that cells develop into the correct tissues and take on the proper function. Autocrine Signaling also regulates pain sensation and inflammatory responses. Further, if a cell is infected with a virus, the cell can signal itself to undergo programmed cell death, killing the virus in the process. In some cases, neighboring cells of the same type are also influenced by the released ligand. In embryological development, this process of stimulating a group of neighboring cells may help to direct the differentiation of identical cells into the same cell type, thus ensuring the proper developmental outcome. Direct Signaling Across Gap Junctions Gap junctions in animals and plasmodesmata in plants are connections between the plasma membranes of neighboring cells. These fluid-filled channels allow small signaling molecules, called intracellular mediators, to diffuse between the two cells. Small molecules, such as calcium ions (Ca 2+ ), are able to move between cells, but large molecules like proteins and DNA cannot fit through the channels. The specificity of the channels ensures that the cells remain independent but can quickly and easily transmit signals.

  Sign up to read

  Learn more about book
• 

  eBook - PDF

  Karp's Cell and Molecular Biology

  • Gerald Karp, Janet Iwasa, Wallace Marshall(Authors)
  • 2021(Publication Date)
  • Wiley

    (Publisher)

  On the other hand, insights into cell signaling can tie together a variety of seemingly independent cellular processes. Cell signaling is also intimately involved in the regulation of cell growth and division. This makes the study of cell signaling crucially important for understanding how a cell can lose the ability to control cell division and develop into a malignant tumor. It may be helpful to begin the discussion of this complex subject by describing a few of the general features that are shared by most signaling pathways. Cells usually communicate with one another through extracellular messenger molecules. Extracellular messengers can travel a short distance and stimu- late cells that are in close proximity to the origin of the message, or they can travel throughout the body, potentially stimulating cells that are far away from the source. In the case of Autocrine Signaling, the cell that is producing the messenger expresses receptors on its surface that can respond to that messenger (Figure 15.1a). Consequently, cells releasing the message will stimulate (or inhibit) themselves. During paracrine signaling (Figure 15.1b), messenger molecules travel only short distances through the extracellular space to cells that are in close prox- imity to the cell generating the message. Paracrine messenger molecules are usually limited in their ability to travel around the body because they are inherently unstable, or they are degraded by enzymes, or they bind to the extracellular matrix. Finally, during endocrine signaling, messenger molecules reach their target cells via passage through the bloodstream (Figure 15.1c). Endocrine messengers, also called hormones, typically act on target cells located at distant sites in the body. An overview of cellular signaling pathways is depicted in Figure 15.2. Cell signaling is initiated with the release of a mes- senger molecule by a cell that is engaged in sending messages to other cells in the body (step 1, Figure 15.2).

  Sign up to read

  Learn more about book
• 

  No longer available |Learn more

  Cell Signaling

  • Wendell A. Lim, Wendell Lim, Bruce Mayer, Tony Pawson(Authors)
  • 2014(Publication Date)
  • Garland Science

    (Publisher)

  And because the signaling apparatus is comprised of biomolecules such as proteins, which are encoded by the genetic material, signaling mechanisms are amenable to the experimen-tal approaches and analytic tools of biochemistry and genetics. oncogenes neuronal signaling cancer biology endocrinology hormone response pathways growth & differentiation pathways immune activation pathways developmental biology neurobiology immunology cell signaling Figure 1.3 Many different fields of research contributed to the current understanding of cell signaling. Research in a wide variety of different disciplines revealed a common set of mechanisms and pathways that provide the basis for diverse biological activities. THE FUNDAMENTAL ROLE OF SIGNALING IN BIOLOGICAL PROCESSES 7 Cancer biology played a particularly important role in the emergence of the field of cell signaling. Our understanding of the molecular basis of can-cer was revolutionized by the discovery of oncogenes , genes that when mutated or overexpressed induce cells to respond inappropriately to nor-mal signals and therefore proliferate uncontrollably, potentially leading to the formation of a malignant tumor (cancer). These oncogenes, once cloned and biochemically characterized, were in most cases found to be constitutively active or otherwise misregulated forms of signaling pro-teins. By understanding how signaling mistakes could lead to cancer, we learned a great deal about the normal signaling mechanisms that regu-late cell proliferation and differentiation. The field of endocrinology focuses on how hormones secreted into the blood, such as insulin, coordinate physiological communication between the different organs and glands that comprise an organism. As research-ers delved into the biochemical basis by which target cells respond to hormones, a similar group of signaling molecules to those found in can-cer biology was uncovered.

  Sign up to read

  Learn more about book
• 

  eBook - ePub

  Physiological Systems in Insects

  • Marc J. Klowden, Marc J Klowden(Authors)
  • 2013(Publication Date)
  • Academic Press

    (Publisher)

  The external signal is thus internalized, amplified, and distributed to several internal targets (Figure 1.1). The chemical signals may consist of many types of molecules, categorized by their range and speed of activity. After the signal is transduced and arrives inside the cell, its target might be either already-synthesized proteins that become activated by the message, or changes in gene expression, either of which can alter cell physiology and behavior (Figure 1.2). Figure 1.1 A signal molecule binds to specific receptor sites on the cell membrane. The activation of the receptor transduces the signal to the cell interior where it is amplified by parallel pathways and distributed to targets. Figure 1.2 Targets of signal transduction in the cell. Cell physiology, metabolism, or behavior may be modified by altered gene expression or altered protein function. Autocrine Signaling is the most private of the signaling modes, with a cell signaling itself by producing a chemical that activates receptors within its own cytoplasm or on its surface (Figure 1.3A). An example is the prothoracic gland, which during some developmental stages activates its own production of ecdysteroids. Figure 1.3 Types of cell signaling. A. Autocrine Signaling. B. Contact-dependent signaling. C. Neuronal signaling. D. Endocrine signaling. E. Paracrine signaling. See the text for an explanation. Contact-dependent signaling relies on direct contact between neighboring cells, with signaling molecules embedded in the cell membranes or passed directly through pores (Figure 1.3B). The signaling cell may produce a molecule that binds to a receptor in the adjacent target cell, or release ions that are transferred through gap junctions to trigger a response only in those cells that are in direct contact. Also called juxtacrine signaling, this is the fastest mode of communication and can be found in cardiac muscle cells whose contractions are coordinated, allowing these to occur simultaneously

  Sign up to read

  Learn more about book
• 

  No longer available |Learn more

  Cell Signaling

  • Wendell A. Lim, Wendell Lim, Bruce Mayer, Tony Pawson(Authors)
  • 2014(Publication Date)
  • Garland Science

    (Publisher)

  Figure 1.3 ). Indeed, the diversity of areas of inquiry that ultimately led to the field of cell signaling underlines the central role of signaling across biology. For example, because signaling is so important to normal physiology, the disruption or misregulation of signaling mechanisms is the basis for many human diseases, and thus these mechanisms are of interest in the areas of medicine and human health. Similarly, because normal development depends on the precise coordination of cell behaviors such as differentiation and movement, research on developmental events necessarily sheds light on the underlying signaling mechanisms. And because the signaling apparatus is comprised of biomolecules such as proteins, which are encoded by the genetic material, signaling mechanisms are amenable to the experimental approaches and analytic tools of biochemistry and genetics

  Figure

  1.3

  Many different fields of research contributed to the current understanding of cell signaling. Research in a wide variety of different disciplines revealed a common set of mechanisms and pathways that provide the basis for diverse biological activities.

  Cancer biology played a particularly important role in the emergence of the field of cell signaling. Our understanding of the molecular basis of cancer was revolutionized by the discovery of oncogenes, genes that when mutated or overexpressed induce cells to respond inappropriately to normal signals and therefore proliferate uncontrollably, potentially leading to the formation of a malignant tumor (cancer). These oncogenes, once cloned and biochemically characterized, were in most cases found to be constitutively active or otherwise misregulated forms of signaling proteins. By understanding how signaling mistakes could lead to cancer, we learned a great deal about the normal signaling mechanisms that regulate cell proliferation and differentiation.

  The field of endocrinology focuses on how hormones secreted into the blood, such as insulin, coordinate physiological communication between the different organs and glands that comprise an organism. As researchers delved into the biochemical basis by which target cells respond to hormones, a similar group of signaling molecules to those found in cancer biology was uncovered. For example, the receptor for insulin, because of its enormous significance to the common human disease diabetes, was one of the first hormone receptors to be cloned. The fact that it was highly related to some of the oncogenic proteins that cause cancer, and had the same biochemical activity (the ability to phosphorylate tyrosine residues on its target substrates), underscored the commonality of signaling mechanisms.

  Sign up to read

  Learn more about book
• 

  eBook - ePub

  Volatile Biomarkers for Human Health

  From Nature to Artificial Senses

  • Hossam Haick(Author)
  • 2022(Publication Date)
  • Royal Society of Chemistry

    (Publisher)

  Part 2: Communication: Volatile Biomarkers as a Signaling Agents Passage contains an image Chapter 9 Signal Transfer and Transduction between Cells

  Mamatha Serasanambatia , Dina Hashoul,b and Hossam Haick,b

  a a Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA;

  b Department of Chemical Engineering and Russell Berrie Nanotechnology Institute, Technion – Israel Institute of Technology, Haifa 3200003, IsraelEmail: [email protected]

  9.1 Introduction

  Cell-to-cell communication has a critical role during tumor development and progression, allowing cancer cells to reprogram the surrounding tumor microenvironment and cells located at distant sites.

  1 ,2

  Cells communicate by several means, nonetheless, with broadly three types of cell communication: autocrine, paracrine and juxtacrine signaling.3 In Autocrine Signaling, a cell secretes a chemical messenger and has the cognate receptor, thereby allowing it to communicate with itself and other cells of the same type. Paracrine signaling involves at least two types of cells: one cell type without the cognate receptor secretes a chemical message, whereas another cell type has the cognate receptor but does not secrete the biomolecule. Lastly, juxtacrine signaling involves two cells in which one cell has a membrane-bound ligand that binds to its cognate receptor on another cell.

  2 –5

  Proteomic and genomic approaches have been the main approaches to study signaling communication in cell proliferation, migration, cell recognition and differentiation.6 Though tremendous advances have been achieved, several limitations restrict the fulfilment of approaches to diagnosis and therapeutic applications. These limitations include but are not confined to:

  5 –9

  (1) proteomics and genomics requiring prior and accurate knowledge of specific genes or proteins, exclusive to in vitro and in vivo trials – something that does not necessarily reflect real-life situations; and (2) genomics and proteomics, which continue to be expensive and of low specificity and which require complex analytical algorithms that are prolonged and cumbersome. Since cancer is a systematic disease (polygenetic) that involves several mutations at different sites8 (genetic, epigenetic, local to or at a distance from the primary tumor, etc.

  Sign up to read

  Learn more about book
• 

  eBook - PDF

  Biology for AP® Courses

  • Julianne Zedalis, John Eggebrecht(Authors)
  • 2018(Publication Date)
  • Openstax

    (Publisher)

  Signaling cells secrete ligands that bind to target cells and initiate a chain of events within the target cell. The four categories of signaling in multicellular organisms are paracrine signaling, endocrine signaling, Autocrine Signaling, and direct signaling across gap junctions. Paracrine signaling takes place over short distances. Endocrine signals are carried long distances through the bloodstream by hormones, and autocrine signals are received by the same cell that sent the signal or other nearby cells of the same kind. Gap junctions allow small molecules, including signaling molecules, to flow between neighboring cells. Internal receptors are found in the cell cytoplasm. Here, they bind ligand molecules that cross the plasma membrane; these receptor-ligand complexes move to the nucleus and interact directly with cellular DNA. Cell-surface receptors transmit a signal from outside the cell to the cytoplasm. Ion channel-linked receptors, when bound to their ligands, form a pore through the plasma membrane through which certain ions can pass. G-protein-linked receptors interact with a G-protein on the cytoplasmic side of the plasma membrane, promoting the exchange of bound GDP for GTP and interacting with other enzymes or ion channels to transmit a signal. Enzyme-linked receptors transmit a signal from outside the cell to an intracellular domain of a membrane-bound enzyme. Ligand binding causes activation of the enzyme. Small hydrophobic ligands (like steroids) are able to penetrate the plasma membrane and bind to internal receptors. Water-soluble hydrophilic ligands are unable to pass through the membrane; instead, they bind to cell-surface receptors, which transmit the signal to the inside of the cell. 9.2 Propagation of the Signal Ligand binding to the receptor allows for signal transduction through the cell. The chain of events that conveys the signal through the cell is called a signaling pathway or cascade.

  Sign up to read

  Learn more about book
• 

  eBook - PDF

  Biomedical Engineering

  Bridging Medicine and Technology

  • W. Mark Saltzman(Author)
  • 2015(Publication Date)
  • Cambridge University Press

    (Publisher)

  Biomedical Engineering: Bridging Medicine and Technology 264 of the co-receptors, which results in the synthesis of various transcription factors that bind to a promoter region upstream of the IL-2 gene. These transcription factors enhance transcription of IL-2. As illustrated in Figure 6.23 , IL-2 is an Autocrine Signaling molecule that stimulates proliferation and differentiation of naïve T cells into armed effector cells: T c or T h cells. 6.5.3 Cytokine signaling As the previous section illustrated, soluble mediator molecules such as cytokines play an important role in adaptive immunity. For example, Autocrine Signaling through IL-2 is required for T-cell activation and proliferation. Paracrine signaling via local secretion of cytokines is used by T cells in the effector phase. An example of paracrine signaling is that of interferon-γ (IFN-γ ). Cytokines secreted by T cells bind to the receptors located on the surface of APCs. Many cytokine receptors are enzyme-linked receptors. In the case of IFN-γ , the interferon receptor is linked to a kinase ( Figure 6.25 ). The kinase is bound to the cytoplasmic domain of the interferon receptor. When IFN-γ binds to its interferon receptor, two monomers dimerize, bringing the associated kinases in closer proximity to each other. The activated kinases phosphorylate a transcription factor, STAT (which stands for Signal Transducers and Activators of Transcrip-tion). The activated STAT dimerizes and translocates (or moves) into the nucleus where it binds to its sites upstream of IFN-γ – responsive genes to activate their transcription. The products of these genes can contribute to multiple effects in the cell expressing the IFN receptor: increased MHC expression and antigen presen-tation, macrophage activation, as well as increased antimicrobial activity and B-cell production of opsonizing antibodies.

  Sign up to read

  Learn more about book