BIOLOGY 171 CHAPTER 11

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BIOLOGY 171CHAPTER 11

• CELL COMMUNICATION

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Cell Signaling An Overview

• Regulation and control is essential at all
  levels of biology.
• Chemicals from the environment and other cells
  are the signaling agents.
• They exert their effect through signal
  transduction or a transduction pathway.

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Cell Signaling Early Evolution

• Chemical Signaling (An Example)
• Coordination of yeast mating behavior.
• a type produces a factor
• b the produces b factor
• The binding of factors to membrane receptors
  of the opposite types causes them to move
  together and to fuse.
• Signal Transduction Pathway - Steps by which a
  signal is converted into a specific cellular
  response.

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Yeast Communication
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Fig. 11-3
Individual rod- shaped cells
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Aggregation in process
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0.5 mm
Spore-forming structure (fruiting body)
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Fruiting bodies
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Location of Communicating Cells

• Local regulators - Work between cells located
  near each other.
• (1)Paracrine or (2)Synaptic Signaling
• Distant Regulators - Impact cells located some
  distance from each other.
• Hormones may be local of distant.
• Examples Insulin, Thyroxin
• Cell to cell junction - Gap junctions and
  plasmodesmata

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CommunicationsLocal and Distant
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Fig. 11-4
Plasma membranes
Gap junctions between animal cells
Plasmodesmata between plant cells
(a) Cell junctions
(b) Cell-cell recognition
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Three Stages of Cell Signaling

• Cells must have the proper signal receptor system
  before a signal can elicit a response.
• Three elements of the signaling system in the
  target cell
• Signal reception
• Signal transduction
• Cellular response
• Example Epinephrine and glycogen metabolism
• Requires intact cells
• Plasma membrane receptor
• Activation of intermediate step/steps inside the
  cell
• Signal transduction
• Activation of glycogen phosphorylase

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Three Stages of Signaling
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Signal Reception/Initiation of Transduction

• Chemical signal, ligand, binds to the
  receptor.
• Most receptors are plasma membrane proteins.
• Causes an alteration of the receptors
  conformation.
• Altered receptor interacts with cellular
  molecules.

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Three Membrane Receptor Families

• 1. G-Protein receptors
• Single polypeptide, threads through membrane,
  seven transmembrane domains.
• Interact with G-proteins on cytoplasmic side
  of membrane.
• Bind to GDP and GTP.
• Binding of GDP inactivates.
• Binding of GTP activates.

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G-Protein Receptors

• Activated G-protein interacts with another
  protein, often an enzyme, thus activating
  enzyme activity.
• Activation of the G-protein is temporary.
• Activated G-protein has GTPase activity which
  hydrolyzes GTP to GDP.
• G-proteins are involved in the regulation of
  many critical metabolic and developmental
  processes.

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G-Protein Structure
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G- ProteinAction
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Three Membrane Receptor Families

• 2. Tyrosine Kinase Receptors
• External receptor and an internal domain with
  tyrosine kinase enzyme activity.
• Two receptor units join together forming a
  receptor dimer
• Dimer formation activates tyrosine kinase
  activity in the cytoplasmic domain.

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Tyrosine Kinase Receptors

• Transfer of phosphate from ATP to tyrosine
  ammo acids in the cytoplasmic domain of the
  receptor.
• Phosphorylation activates a relay protein
• Initiation of a transduction system
• Cellular response.
• Many different proteins may be activated
• Dephosphorylation of the tyrosine kinase
  receptor results in the termination of the
  signal process.

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Fig. 11-7c
Ligand-binding site
Signaling molecule (ligand)
Signaling molecule
? Helix
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyrosines
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosine kinase proteins
Dimer
CYTOPLASM
1
2
Activated relay proteins
Cellular response 1
Tyr
P
P
Tyr
Tyr
Tyr
P
Tyr
Tyr
P
Tyr
Tyr
P
P
Tyr
P
Tyr
Tyr
Tyr
P
Cellular response 2
P
P
Tyr
Tyr
P
Tyr
Tyr
Tyr
Tyr
P
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ATP
6 ADP
Activated tyrosine kinase regions
Fully activated receptor tyrosine kinase
Inactive relay proteins
3
4
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Three Membrane Receptor Families

• 3. Ion-Channel Receptors
• Signal proteins binds to a gated ion channel
• Ion channel proteins are for a specific ion
  such as Na, Ca2 or K
• -------------------------------------------------
  -------------------
• Receptors may be intracellular
• Hormones like progesterone, testosterone,
  estradiol and thyroid hormones.

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1
Signaling molecule (ligand)
Gate closed
Ions
Ion Channel Receptors
Plasma membrane
Ligand-gated ion channel receptor
2
Gate open
Cellular response
3
Gate closed
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Fig. 11-9
Signaling molecule
Receptor
Activated relay molecule
Inactive protein kinase 1
Active protein kinase 1
Inactive protein kinase 2
ATP
Phosphorylation cascade
ADP
P
Active protein kinase 2
PP
P
i
Inactive protein kinase 3
ATP
ADP
P
Active protein kinase 3
PP
P
i
Inactive protein
ATP
P
ADP
Active protein
Cellular response
PP
P
i
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Signal Amplification
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Signal Specificity

• Signal Impact on Different Cells
• Epinephrine on liver cells.
• Epinephrine on cardiac
• muscle.

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Signal Transduction Pathways

• The signal is relayed through a series of
  steps from receptor to target molecule.
• The signal molecule is not passed along the
  transduction pathway.
• Protein phosphorylation is a common method of
  signal transduction.

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Signal Transduction PathwaysProtein
Phosphorylation

• Cytoplasmic protein kinases facilitate the
  transfer of phosphate from ATP to other
  proteins some of which may be enzymes.
• Phosphorylation may serve to activate an
  enzyme or to inactivate it.  
• The signal transduction pathway is turned off
  when the signal is no longer present. 
• Protein phosphatases can reverse the effects
  of protein kinases.

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Phosphorylation Cascade
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Second Messengers
Small, non-protein water soluble molecules and
ions that propagate signals. Cyclic AMP -
cAMP cAMP - second messenger of several
hormones. cAMP related transduction pathway
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cAMP Related Transduction Pathway

• Ligand (signal) binds to the receptor. 
• G-protein on the inside of the membrane is
  activated by the receptor.
• The activated G-protein activates the enzyme,
  adenylyl cyclase, which converts ATP to cAMP.
• cAMP activates a cytoplasmic enzyme such as a
  protein kinase.
• The protein kinase propagates the signal by
  phosphorylating various proteins.

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cAMP
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cAMP Second Messenger
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Calcium Ions and Inositol Triphosphate

• An increase in calcium ion concentration is
  important in inducing a specific response from
  a transduction system. 
• Ca2 concentration can be affected in two ways.
• The binding of a ligand to a Ca2 gated ion
  channel protein. (Already Shown)
• Activation of the inositol triphosphate (IP3)
  signaling pathway.

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The IP3 Pathway

• Signal (ligand) binds to the membrane receptor.
• Activation of phospholipase, enzyme located on
  the cytoplasmic side of the membrane.
• Activated enzyme hydrolyzes membrane
  phospholipids into IP3 and diacylglycerol.
• Diacylglycerol - is associated with a different
  protein kinase pathway.

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The IP3 PathwayTwo Modes of Operation

• IP3 is associated with Ca2 signaling pathways. 
• IP3 binds to Ca2 gated channel proteins. 
• IP3 binding causes a release of Ca2
• Activate target proteins or
• Ca2 binds to a relay protein, calmodulin,
  which modulates the activity of specific
  target proteins.

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The IP3 Pathway
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Cellular Responses to Signals

• Regulate metabolic activity in the cytoplasm
• Regulate transcription in the nucleus
• Signals affect cytoplasmic activity by
  regulating the function or activity of proteins.
• Rearrangement of the cytoskeleton.
• Regulating ion channels.
• Regulate critical points in metabolic pathways.
• Signals affect on the nucleus
• Modulating the expression of specific genes
• at various levels.

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Nuclear Control
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Amplification and Specificity

• Signal Amplification
• Signal Specificity