Cell Communication

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Cell Communication

• Chapter 7

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7.1 Cell Communication An Overview

• Cells communicate with one another through
• Direct channels of communication
• Specific contact between cells
• Intercellular chemical messengers

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Apoptosis

Fig. 7-1, p. 140
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Intercellular Chemical Messengers

• Controlling cell
• Releases signal molecule that causes response of
  target cells
• Target cell processes signal in 3 steps
• Reception, transduction, response
• Signal transduction
• Series of events from reception to response

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Signal Transduction

Fig. 7-2, p. 142
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Reception

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7.2 Cell Communication Systems with Surface
Receptors

• Peptide hormones and neurotransmitters
• Primary extracellular signal molecules recognized
  by surface receptors in animals
• Surface receptors
• Integral membrane glycoproteins
• Signaling molecule
• Bound by a surface receptor
• Triggers response pathways within the cell

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Surface Receptors

• Cell communication systems based on surface
  receptors have 3 components
• (1) Extracellular signal molecules
• (2) Surface receptors that receive signals
• (3) Internal response pathways triggered when
  receptors bind a signal

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Peptide Hormones

• Peptide hormones
• Small proteins
• Growth factors
• Special class of peptide hormones
• Affect cell growth, division, differentiation

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Neurotransmitters

• Neurotransmitters include
• Small peptides
• Individual amino acids or their derivatives
• Chemical substances

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Surface Receptors

• Surface receptors
• Integral membrane proteins
• Extend entirely through the plasma membrane
• Binding of a signal molecule
• Induces molecular change in the receptor that
  activates its cytoplasmic end

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Response of Surface Receptor

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Cellular Response Pathways (1)

• Cellular response pathways
• Operate by activating protein kinases
• Protein kinases add phosphate groups
• Stimulate or inhibit activities of target
  proteins, producing cellular response

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Cellular Response Pathways (2)

• Protein phosphatases
• Reverse response
• Remove phosphate groups from target proteins
• Receptors are removed by endocytosis
• When signal transduction is finished

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Phosphorylation

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Amplification

• Each step of a response pathway catalyzed by an
  enzyme is amplified
• Each enzyme activates hundreds or thousands of
  proteins that enter next step in pathway
• Amplification
• Allows full cellular response when few signal
  molecules bind to receptors

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Amplification

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7.3 Surface Receptors with Built-In Protein
Kinase Activity

• Receptor Tyrosine Kinases

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Receptor Tyrosine Kinases

• Receptor tyrosine kinases bind signal molecule
• Protein kinase site becomes active
• Adds phosphate groups to tyrosines in the
  receptor itself, and to target proteins
• Phosphate groups added to cytoplasmic end of
  receptor are recognition sites for proteins
  activated by binding to the receptor

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Protein Kinase Activity

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7.4 G-ProteinCoupled Receptors

• G proteins Key molecular switches in
  second-messenger pathways
• Two major G-proteincoupled receptor response
  pathways involve different second messengers

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G-Protein-Coupled Receptors

• G-protein-coupled receptors activate pathways
• Binding of the extracellular signal molecule
  (first messenger) activates a site on the
  cytoplasmic end of the receptor

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G-Protein-Coupled Receptors

Fig. 7-8, p. 147
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G-Protein Activation

• Activated receptor turns on a G protein, which
  acts as a molecular switch
• G protein
• Active when bound to GTP
• Inactive when bound to GDP

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Active G Protein

• Active G protein
• Switches on the effector of the pathway (enzyme
  that generates second messengers)
• Second messengers
• Small internal signal molecules
• Activate the protein kinases of the pathway

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Response Pathways

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Second Messengers cAMP

• 1st of two major pathways triggered by
  G-protein-coupled receptors
• Effector (adenylyl cyclase) generates cAMP as
  second messenger
• cAMP activates specific protein kinases

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cAMP Receptor-Response Pathways

Fig. 7-10, p. 148
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cAMP

Fig. 7-11, p. 148
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Second Messengers IP3 and DAG (1)

• 2nd major pathway triggered by G-proteincoupled
  receptors
• Activated effector (phospholipase C), generates
  two second messengers, IP3 and DAG

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Second Messengers IP3 and DAG (2)

• IP3 activates transport proteins in the ER
• Releasing stored Ca2 into the cytoplasm
• Released Ca2 (alone or with DAG) activates
  specific protein kinases
• Adds phosphate groups to target proteins

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IP3/DAG Receptor-Response Pathways

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Pathway Controls

• cAMP and IP3/DAG pathways are balanced by
  reactions that eliminate second messengers
• Stopped by protein phosphatases that continually
  remove phosphate groups from target proteins
• Stopped by endocytosis of receptors and their
  bound extracellular signals

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Mutations

• Mutated systems can turn on the pathways
  permanently, contributing to progression of some
  forms of cancer

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Gene Regulation Ras

• Some pathways in gene regulation link certain
  receptor tyrosine kinases to a specific G protein
  (Ras)
• When the receptor binds a signal molecule, it
  phosphorylates itself
• Adapter proteins then bind, bridging to and
  activating Ras

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Activated Ras

• Activated Ras turns on the MAP kinase cascade
• Last MAP kinase in cascade phosphorylates target
  proteins in the nucleus
• Activates them to turn on specific genes
• Many of these genes control cell division

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Gene Regulation

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7.5 Pathways Triggered by Internal Receptors
Steroid Hormone Receptors

• Steroid hormones have widely different effects
• Depend on relatively small chemical differences
• Response of a cell to steroid hormones
• Depends on internal receptors and the genes they
  activate

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Steroid Hormone Receptors

• Steroid hormones penetrate plasma membrane
• Bind to receptors within the cell
• Internal receptors
• Regulatory proteins that turn on specific genes
  when activated by binding a signal molecule
• Produce cellular response

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Two Domains of Steroid Hormone Receptors

• Steroid hormone receptors
• One domain recognizes and binds a specific
  steroid hormone
• One domain interacts with the controlling regions
  of target genes

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Gene Activation Steroid Hormone Receptors

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Cell Response

• Cell response to a steroid hormone
• Depends on whether it has an internal receptor
  for the hormone
• Type of response within the cell
• Depends on the genes that are recognized and
  turned on by an activated receptor

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7.6 Integration of Cell Communication Pathways

• Cross talk

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Cross-Talk

• Cell signaling pathways communicate with one
  another to integrate responses to cellular
  signals
• May result in a complex network of interactions
  between cell communication pathways

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Cross-Talk

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Modification of Cell Response

• Cross-talk often results in
• Modifications of cellular responses controlled by
  the pathways
• Fine-tuning effects of combinations of signal
  molecules binding to receptors of a cell

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Cell Communication PathwaysIn Animals

• Inputs from other cellular response systems also
  can become involved in the cross-talk network
• Cell adhesion molecules
• Molecules arriving through gap junctions