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Cell Signaling Mechanisms by 1L72T6

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									                  Cell Signaling Mechanisms

 Learning Objectives
 At the end of the lecture student should be able to
  understand;

   Describe the Significance of cell signaling
   Discuss types of intracellular communication
   Explain First and second messengers
   Describe Four features of signal transducing system
   Describe the activation of second messenger system
   Explain the activation of calcium second messenger system

 Cell Signaling: Responding to the outside world

 Cells interact with their environment by interpreting
  extracellular signals via proteins that span their plasma
  membrane called receptors

 Receptors are comprised of extracellular and
  intracellular domains

 The extracellular domain relays information about the
  outside world to the intracellular domain

 Cell Signaling: responding to the outside world

 The intracellular domain then interacts with other
  intracellular signaling proteins

 These intracellular signaling proteins further relay the
  message to one or more effector proteins

 Effector proteins mediate the appropriate response
 Cell Signaling: responding to the outside world

 This event is transduced into secondary responses
  within the cell that can be divided into four broad
  categories:

   ion channel activation,
   G-protein activation,
   activation of enzyme activity within the cell,
   direct activation of transcription

 Some signals to which cell respond






 Cell surface receptors
 Signaling molecules include peptide hormones, catechol-
  amines, insulin, growth factors, cytokines, etc

 Binding, and subsequent events, triggers an  or  in the
  cytosolic concentration of a second messenger; or the
  activated,bound receptor acts as a scaffold to recruit and
  activate other intracellular proteins




 Intracellular Receptors
 Signaling molecules include steroid hormones,
  retinoids,thyroxine, etc

 Receptor-hormone complex acts a transcription factor to
  alter transcription of certain genes

 Receptor Characteristics
 Participates in transduction of the signal from the
  external messenger to some component of the
  metabolic machinery

 Has at least one additional functional site which is
  altered by ligand binding (allosteric site)

 Extracellular ligands are called "first messengers" and
  the intracellular mediators are called "second
  messengers."
 Four features of signal transducing
  system




 Advantages





 Each cell is programmed to respond to specific combinations
  of signaling molecules

 Different cells can respond differently to the same chemical
  signal

 Six general types of signal transducers





 Categories
 Peptides or polypeptides - insulin, glucagon, growth
  hormone, insulin-like growth factors, vasopressin,
  prolactin….

 Glycoproteins - follicle stimulating hormone (FSH), thyroid
  stimulating hormone (TSH)…

 Steroids - glucocorticoids (aldosterone, cortisol), steroids
  (progesterone, testosterone), retinoic acid…

 Amino acid derivatives - epinephrine, norepinephrine,
  thyroxine, triidothyronine


 AGONISTS vs. ANTAGONISTS
 Agonist         mimics a hormone in binding
  productively to a receptor
 Antagonist     mimics a hormone stereochemically, but
  binds to the receptor
           non-productively, inhibiting the action of the
  natural hormone






 Three largest classes of cell surface receptors



 Ion Channel linked receptor





 G protein-
  linked
  Membrane
  Receptors
 e.g.
  Glucagon,
  Epinephrine
  and
  Thrombin as
  signaling
  molecules
 Activates a
  chain of events  alterations in concentrations of
  signaling molecules;

    elaborate sets of interacting molecules that can relay
    signals from cell surface to the nucleus

 Components:

 Receptor; Transducer (G protein):

 Effector (membrane-bound enzyme);

 Second messenger (e.g. cAMP);

 Response (cascade of highly-regulated protein
  phosphorylations, etc
 Characteristics of G proteins
 G protein is an  trimeric protein which binds guanine
  nucleotides
 They function to couple integral membrane receptors to
  target membrane-bound enzymes
 They can be considered molecular switches where in
  GDP (inactive)  GTP (active) + 
 . The dissociated  subunit expresses GTPase activity.





 Enzyme linked cell surface receptor
 Phospholipase C mechanism






 Hormonal involvement in responses to a stimulus



    Ca+2 acting as an intracellular receptors
    Cells must work very hard to maintain low intracellular
    [Ca2+]
    in order for Ca2+ to result in effective intracellular
    signaling.

								
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