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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-Protein–Coupled Receptors
G proteins: Key molecular switches in second-messenger pathways
Two major G-protein–coupled 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-protein–coupled 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