Chapter 9
Cellular Signaling
Lecture Presentations by
Nicole Tunbridge and
© 2021 Pearson Education Ltd. Kathleen Fitzpatrick
Figure 9.1a
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Figure 9.1b
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CONCEPT 9.1: External signals are converted to
responses within the cell
• Ancestral signaling molecules likely evolved in
prokaryotes and single-celled eukaryotes and were
adopted for use in their multicellular descendants
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Evolution of Cell Signaling
• Research in the 1970s suggested that bacterial
cells were capable of signaling to each other
• Cell signaling is critical among prokaryotes
• A concentration of signaling molecules allows
bacteria to sense local population density in a
process called quorum sensing
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• An example of quorum sensing is the formation of a
biofilm
• A biofilm is an aggregation of bacterial cells
adhered to a surface
• Another example of medical importance is the
secretion of toxins by infectious bacteria
• Interfering with the signaling pathways used in
quorum sensing may be a promising approach as
an alternative to antibiotic treatment
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Figure 9.2
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• The yeast Saccharomyces cerevisiae has two
mating types, a and α
• Cells of different mating types locate each other via
secreted factors specific to each type
• The binding of a mating factor at the cell surface
initiates a series of steps called a signal
transduction pathway
• Molecular details of signal transduction in yeasts
and mammals are very similar.
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Figure 9.3
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Local and Long-Distance Signaling
• Cells in a multicellular organism communicate via
signaling molecules
• In local signaling, animal cells may communicate by
direct contact
• Animal and plant cells have cell junctions that
directly connect the cytoplasm of adjacent cells
• Signaling substances in the cytosol can pass
between adjacent cells
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• Animal cells may also communicate by direct
contact between cell-surface molecules
• Local signaling is especially important in embryonic
development, immune response, and maintaining
adult stem cell populations
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Figure 9.4
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• In other cases, animal cells communicate using
secreted messenger molecules that travel only
short distances
• This type of local signaling in animals is called
paracrine signaling
• Growth factors, which stimulate nearby target cells
to grow and divide, are one class of such local
regulators in animals
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• Synaptic signaling occurs in the animal nervous
system when a neurotransmitter is released in
response to an electric signal
• Drugs used to treat depression, anxiety, and post-
traumatic stress disorder (PT S D) affect this
signaling process
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• In long-distance signaling, plants and animals use
molecules called hormones
• In hormonal (or endocrine) signaling in animals
specialized cells release hormones, which travel to
target cells via the circulatory system
• The ability of a cell to respond to a signal depends
on whether or not it has a receptor specific to that
signal
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Figure 9.5
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The Three Stages of Cell Signaling: A Preview
• Earl W. Sutherland and colleagues discovered how
the hormone epinephrine acts on cells
• Sutherland’s work suggested that cells receiving
signals went through three processes
– Signal Reception
– Signal Transduction
– Cellular Response
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• In reception, the target cell detects a signaling
molecule that binds to a receptor protein on the cell
surface
• In transduction, the binding of the signaling
molecule alters the receptor and initiates a signal
transduction pathway; transduction often occurs
in a series of steps
• In response, the transduced signal triggers a
specific response in the target cell
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Figure 9.6
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Animation: Overview of Cell Signaling
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CONCEPT 9.2: Reception: A signaling molecule
binds to a receptor protein, causing it to change
shape
• The binding between a signal molecule (ligand)
and receptor is highly specific
• A shape change in a receptor is generally the initial
transduction of the signal
• Most signal receptors are plasma membrane
proteins, but others are located inside the cell
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Receptors in the Plasma Membrane
• G protein-coupled receptors (G P C R s) are the
largest family of cell-surface receptors
• Most water-soluble signal molecules bind to
specific sites on receptor proteins that transmit
information from the extracellular environment to
the inside of the cell
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Figure 9.7
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• There are three main types of membrane receptors:
– G protein-coupled receptors
– Receptor tyrosine kinases
– Ion channel receptors
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• G protein-coupled receptors (G P C R s) are
cell-surface transmembrane receptors that work
with the help of a G protein
• G proteins bind the energy-rich G T P
• G proteins are all very similar in structure
• G P C R systems are extremely widespread and
diverse in their functions
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Figure 9.8a
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Figure 9.8b
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• Receptor tyrosine kinases (R T K s) are
membrane receptors that catalyze the transfer of
phosphate groups from AT P to another protein
• A receptor tyrosine kinase can trigger multiple
signal transduction pathways at once
• Abnormal functioning of R T K s is associated with
many types of cancers
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Figure 9.8c
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• A ligand-gated ion channel receptor acts as a
gate that opens and closes when the receptor
changes shape
• When a signal molecule binds as a ligand to the
receptor, the gate allows specific ions, such as Na+
or Ca2+, through a channel in the receptor
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Figure 9.8d
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Intracellular Receptors
• Intracellular receptor proteins are found in the
cytoplasm or nucleus of target cells
• Small or hydrophobic chemical messengers can
readily cross the membrane and activate receptors
• Examples of hydrophobic messengers are the
steroid and thyroid hormones of animals
• An activated hormone-receptor complex can act as
a transcription factor, turning on or off specific
genes
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Figure 9.9
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CONCEPT 9.3: Transduction: Cascades of
molecular interactions transmit signals from
receptors to relay molecules in the cell
• Cell signaling is usually a multistep process
• Multistep pathways can greatly amplify a signal
• Multistep pathways provide more opportunities for
coordination and regulation of the cellular response
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Signal Transduction Pathways
• The binding of a signaling molecule to a receptor
triggers the first step in a chain of molecular
interactions
• The activated receptor activates another protein,
which activates another, and so on, until the protein
producing the response is activated
• At each step, the signal is transduced into a
different form, commonly a shape change in a
protein
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Protein Phosphorylation and
Dephosphorylation
• Phosphorylation and dephosphorylation of proteins
are commonly used in cells to regulate protein
activity
• Protein kinases transfer phosphates from AT P to
protein, a process called phosphorylation
• Many relay molecules in signal transduction
pathways are protein kinases, creating a
phosphorylation cascade
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Figure 9.10
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• Protein phosphatases rapidly remove the
phosphates from proteins, a process called
dephosphorylation
• This phosphorylation and dephosphorylation
system acts as a molecular switch, turning activities
on and off, or up or down, as required
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Small Molecules and Ions as Second
Messengers
• Many signaling pathways involve second
messengers
• These are small, nonprotein, water-soluble
molecules or ions that spread throughout a cell by
diffusion
• Second messengers participate in pathways
initiated by G P C R s and R T K s
• Cyclic AM P and calcium ions are common second
messengers
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Cyclic AM P
• Cyclic AM P (cAM P), a small molecule produced
from AT P, is one of the most widely used second
messengers
• Adenylyl cyclase, an enzyme in the plasma
membrane, converts AT P to cAM P in response to
an extracellular signal
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Figure 9.11
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• Many signal molecules trigger formation of cAM P
• Other components of cAM P pathways are G
proteins, G protein-coupled receptors, and protein
kinases
• cAM P usually activates protein kinase A, which
phosphorylates various other proteins
• Further regulation of cell metabolism is provided by
G protein systems that inhibit adenylyl cyclase
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Figure 9.12
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• Understanding of the role of cAM P in G protein
signaling pathways helps explain how certain
microbes cause disease
• The cholera bacterium, Vibrio cholerae, produces a
toxin that modifies a G protein so that it is stuck in
its active form
• This protein continually makes cAM P, causing
intestinal cells to secrete large amounts of salt into
the intestines
• Water follows by osmosis, and an untreated person
can soon die from loss of water and salt
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Calcium Ions and Inositol Triphosphate (I P3)
• Calcium ions (Ca2+) are used widely as a second
messenger; even more so than cAM P
• Ca2+ can function as a second messenger because
its concentration in the cytosol is normally much
lower than the concentration outside the cell
• A small change in number of calcium ions thus
represents a relatively large percentage change in
calcium concentration
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Figure 9.13
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• A signal relayed by a signal transduction pathway
may trigger an increase in calcium in the cytosol
• Pathways leading to the release of calcium involve
inositol triphosphate (I P3) and diacylglycerol
(D AG) as additional second messengers
• These two are produced by cleavage of a certain
kind of phospholipid in the plasma membrane
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Figure 9.14
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Animation: Signal Transduction Pathways
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CONCEPT 9.4: Cellular response: Cell signaling
leads to regulation of transcription or
cytoplasmic activities
• The cell’s response to an extracellular signal is
called the “output response”
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Nuclear and Cytoplasmic Responses
• Ultimately, a signal transduction pathway leads to
regulation of one or more cellular activities
• The response may occur in the nucleus or in the
cytoplasm
• Many signaling pathways regulate the synthesis of
enzymes or other proteins, usually by turning genes
on or off in the nucleus
• The final activated molecule in the signaling
pathway may function as a transcription factor
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Figure 9.15
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• Other pathways may regulate the activity of
proteins rather than their synthesis
• For example, a signal could cause opening or
closing of an ion channel in the plasma membrane
or a change in the activity of a metabolic enzyme
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Figure 9.16
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• Signal receptors, relay molecules, and second
messengers participate in a variety of pathways,
leading to nuclear and cytoplasmic responses,
including cell division
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Regulation of the Response
• A response to a signal may not be simply “on” or
“off”
• There are four aspects of signal regulation:
– Amplification of the signal (and thus the response)
– Specificity of the response
– Overall efficiency of response, enhanced by
scaffolding proteins
– Termination of the signal
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Signal Amplification
• Enzyme cascades amplify the cell’s response to the
signal
• At each step, the number of activated products can
be much greater than in the preceding step
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The Specificity of Cell Signaling and
Coordination of the Response
• Different kinds of cells have different collections of
proteins
• These different proteins allow cells to detect and
respond to different signals
• The same signal can have different effects in cells
with different proteins and pathways
• Pathway branching and “cross-talk” further help the
cell coordinate incoming signals
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Figure 9.17
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Signaling Efficiency: Scaffolding Proteins and
Signaling Complexes
• Scaffolding proteins are large relay proteins to
which several other relay proteins are attached
• Scaffolding proteins can increase the signal
transduction efficiency by grouping together
different proteins involved in the same pathway
• In some cases, scaffolding proteins may also help
activate some of the relay proteins
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Figure 9.18
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Termination of the Signal
• Inactivation mechanisms are an essential aspect of
cell signaling
• If the concentration of external signaling molecules
falls, fewer receptors will be bound
• Unbound receptors revert to an inactive state
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CONCEPT 9.5: Apoptosis requires integration
of multiple cell-signaling pathways
• Cells that are infected, damaged, or at the end of
their functional lives often undergo “programmed
cell death”
• Apoptosis is the best-understood type
• Components of the cell are chopped up and
packaged into vesicles that are digested by
scavenger cells
• Apoptosis prevents enzymes from leaking out of a
dying cell and damaging neighboring cells
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Figure 9.19
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Apoptosis in the Soil Worm Caenorhabditis
elegans
• In worms and other organisms, apoptosis is
triggered by signals that activate a cascade of
“suicide” proteins in the cells destined to die
• In C. elegans, a protein called Ced-9,in the outer
mitochondrial membrane serves as a master
regulator of apoptosis
• Ced-9 acts as a brake in the absence of a signal
promoting apoptosis
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• When the death signal is received, an apoptosis-
inhibiting protein (Ced-9) is inactivated, which
disables the “brake”
• The apoptotic pathway activates proteases and
nucleases, that cut up proteins and D NA of the cell
• The chief caspase in the nematode is called Ced-3
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Figure 9.20
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Apoptotic Pathways and the Signals That
Trigger Them
• In humans and other mammals, several different
pathways, involving about 15 caspases, can carry
out apoptosis
• Apoptosis can be triggered by signals from outside
the cell or inside it
• Internal signals can result from irreparable D NA
damage or excessive protein misfolding
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• Apoptosis evolved early in animal evolution and is
essential for the development and maintenance of
all animals
• For example, apoptosis is a normal part of
development of hands and feet in humans (and
paws in other mammals)
• Apoptosis may be involved in some diseases (for
example, Parkinson’s and Alzheimer’s);
interference with apoptosis may contribute to some
cancers
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Figure 9.21
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Figure 9.UN01
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Figure 9.UN02
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Figure 9.UN03
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