Fundamentals of Cell Biology by bes0Ttrq

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									Fundamentals of Cell Biology

Chapter 11: Signal Transduction
 and Cellular Communication
   Chapter Summary: The Big Picture (1)

• Chapter foci:
  – Structure of a signaling pathway
  – Types of signals cells detect and the role of the
    receptor
  – Molecules most commonly found in signaling
    pathways
  – Examples of well known signaling pathways
    examined in order to understand all of the
    aforementioned
Chapter Summary: The Big Picture (2)

• Section topics:
  – Signaling molecules form communication
    networks
  – Cell-signaling molecules transmit information
    between cells
  – Intracellular signaling proteins propagate
    signals within a cell
  – A brief look at some common signaling
    pathways
     Signaling molecules form communication
                    networks
• Key Concepts:
  – Signaling networks relay information from the
    extracellular environment to the interior of a cell.
  – The basic unit of a signaling network is a signal
    transduction pathway, which carries one specific
    signal in a single direction from the source (a
    receptor) to the effector.
  – Most signal transduction pathways are comprised of
    several different molecules that activate each other
    in a carefully controlled sequence of binding
    interactions.
               Signal Transduction Pathway

•   function: convert
    extracellular information
    into an appropriate
    cellular response
•   composed of:
      – signals
      – receptors
      – signaling proteins
      – second messenger
         molecules

        Figure 11.01:
           Simple
        schematic of
            signal
        transduction
          pathways.
          Signal Transduction Pathway




Figure 11.02: Signaling pathways use linear, convergent, divergent, and branched signaling pathways to
                            generate complex responses to external signals.
Signaling networks are long and
            complex
        Cell-signaling molecules transmit
           information between cells
• Key Concepts:
  – Signals arise from the extracellular space, and
    must bind a receptor to be effective.
  – Most signals are molecules that cannot penetrate
    the plasma membrane, so they bind to receptor
    proteins on the cell surface. Those signals can
    then pass through membranes and are bound by
    receptors in the cytosol.
  – Receptors are grouped into six classes, according
    to their structure, binding partners, and cellular
    location.
 Signaling begins when ligand binds to
            target receptor
• Types of ligands:
   – Membrane impermeable
      • neurotransmitters
   – Membrane permeable
      • estrogen, testosterone
   – Physical signals
      • pressure, temperature, light
6 classes of receptors detect a vast array of environmental stimuli




     Figure 11.03:
     Receptors are
   grouped into six
   classes based on
    their structure
      and cellular
       location.
G-protein coupled receptors activate G proteins




   Figure 11.04: The general structure of a seven transmembrane receptor.
Receptor protein kinases phosphorylate signaling proteins




                                          Figure 11.05: Model of
                                          growth factor receptor
                                                activation.
Receptor protein kinases phosphorylate signaling proteins


                                                Figure 11.06:
                                           Serine/threonine kinase
                                         receptor activation leads to
                                            phosphorylation of a
                                              signaling protein.
Figure 01.14C: The 20 most common amino acids are classified into three classes
                  based on the structure of their side chains.
Phosphoprotein phosphatases remove phosphate groups from
                    signaling proteins




Figure 11.07: Protein phosphatases break the phosphester bond linking phosphate groups
                       to serine, threonine, and tyrosine side chains.
Guanylyl cyclases produce the signaling molecule cyclic GMP




                                     Figure 11.08: Receptor guanylyl
                                        cyclases are homodimeric
                                         receptors that contain a
                                         cytoplasmic domain that
                                      converts GTP into cyclic GMP.
Ion channel receptors permit ion fluxes
                                   Figure 11.09:
                                   Ligand-gated
                                channels typically
                                  form a central
                                 pore that opens
                                  when a ligand
                                   binds to the
                                     receptor.
Transmembrane scaffolds recruit intracellular signaling proteins




                                                         Figure 11.10:
                                                            Integrin
                                                        receptors form
                                                           signaling
                                                           scaffolds.
Nuclear receptors are transcription factors




                                Figure 11.11: The steroid
                                receptor binds to steroid
                              hormones when they diffuse
                                    into the cytosol.
  Intracellular signaling proteins propagate
              signals within a cell
• Key Concepts:
  – Signaling proteins rapidly transmit and amplify
    signal information.
  – As information passes through a signal transduction
    pathway, it often changes physical form.
  – Signaling proteins are grouped into six classes
    based on their structure, location, and mechanism of
    signal transmission.
  – Second messengers are non-protein molecules that
    link signaling proteins together in signal transduction
    pathways.
      G proteins are molecular switches




Figure 11.12: The GTPase cycle repeats continuously, shifting the G protein between active
                             and inactive states like a switch.
G proteins are molecular switches



                            Figure 11.13: A
                           heterotrimeric G
                        protein signaling cycle.
GTPase cycle
          Protein kinases phosphorylate
          downstream signaling proteins




Figure 11.14: Protein kinases add phosphate groups to signaling proteins and effectors.
Lipid kinases phosphorylate phopsholipids




Figure 11.15: Lipid kinases add phosphates to phospholipids.
Calcium fluxes control calcium-binding proteins




                                   Figure 11.16: Calmodulin is
                                     an example of a calcium
                                   sensitive signaling protein.
      Adenylyl cyclases form cyclic AMP



                                                              Figure 11.18:
                                                           Phosphodiesterase
                                                               cleaves the
                                                           phosphoester bond
                                                              between the
                                                          phosphate and the 3'
                                                            carbon of ribose,
Figure 11.17: Adenylyl cyclase is a target of competing
                                                           converting cAMP to
                regulatory pathways.
                                                                  AMP.
Adaptors facilitate binding of multiple signaling proteins
                            Signaling, an overview
                                                       Ligand
                            Guanylyl         Scaffold Gated Ion
                      S/TKR Cyclase         (Integrin) Channel
             RTK                                                        Steroids
   GPCR

                                   Signaling
                                   Proteins
Hetero-    Protein     Lipid     Calcium     Adenylyl   Adaptor Mono-
trimeric G Kinases    Kinases    Binding     Cyclases   Proteins meric G
Proteins                         Proteins                        Proteins

                                    Second
                                   Messengers
                                                                        Steroid
                                  Lipids +        Nucleotides
                     Ions                                              Receptors
                                Hydrocarbons
                 iClicker Time
What causes the α and βγ subunits of heterotrimeric G
proteins to dissociate from each other?

a.    Phosphorylation of the α subunit
b.    Phosphorylation of the G protein-linked receptor
c.    Phosphorylation of GEF
d.    A change in shape in G protein linked receptors
e.    Cleavage of GTP to GDP by the α subunit.
    A brief look at some common signaling
                    pathways
• Key Concepts:
   – Hundreds of different receptors, signaling proteins, and
     effectors combine into a complex network of interacting
     pathways within a single cell.
   – Despite the tremendous complexity of signaling
     networks, many share common features that help set
     the standard for our current understanding of how signal
     transduction pathways function.
   – Some signal transduction pathways trigger short-term
     cellular changes via very long and complex sets of
     signaling interaction, while others contain very few steps
     and have relatively long-term effects on cells.
  Protein tyrosine kinase signaling pathways control
               cell growth and migration




Figure 11.19: A simplified version
   of an FGF signaling pathway.
Heterotrimeric G protein signaling pathways regulate a
          great variety of cellular behaviors




                             Figure 11.20: A sample cAMP signaling
                                            pathway.
Phospholipid kinase pathways work in cooperation
  with protein kinase and G protein pathways




Figure 11.21: The phosphoinositol 4,5-bis phosphate (PIP2) signaling pathway.
Phospholipid kinase pathways work in cooperation
  with protein kinase and G protein pathways




                                      Figure 11.22: PIP2
                                  phosphodiesterase and IP3
                                   phosphatase inhibit PIP2
                                          signaling.

								
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