Fire on the
Mountain
C HA P TE R 1 6
C e l l C o mmu n i c a t i o n
( S i g n a l i n g a n d
S i g n a l T r a n s d u c t i o n )
Cell communication (signaling using extracellular
molecules) is critically important to both unicellular and
multicellular organisms
Fig 16-1 Response
to mating factor in
yeast
Early embryos of
the sea hare Aplysia
Cell signaling and signal transduction
I. The main idea
A. Cells communicate using extracellular signals
B. Three steps in cell signaling
1. Signal reception
2. Signal transduction
3. Response
C. Types of responses depend on the final effector protein in the pathway
1. Rapid and reversible
a. Allosteric enzyme target metabolic change
b. Cytoskeleton target change in cell shape or motility
c. Transport protein target change in cell or organelle permeability
2. Slower and less reversible:
Transcription regulator target change in gene expression
D. There are a variety of different signal-delivery systems
E. Coordination
1. Same signal, different responses in different cells
2. Same cell, different responses to different combinations of signals
D. F. Quickly inactivating signaling pathways is as important as turning them on
Fig 16-12
Signals bind to receptors
that change conformation to
initiate signal transduction
pathways
Signal transduction pathways
end at effector proteins that
mediate the appropriate
response to the signal
Fig 16-7 Signals bind to receptors that change conformation to
initiate signal transduction pathways
Signal transduction
pathways end at effector
proteins that mediate the
appropriate response to
the signal
What makes one cell a target for a signal while
other cells ignore that signal?
The presence of the
receptor molecule
What determines the type of response the cell
will have? (Different cells may respond
differently to the same signal)
The nature of the
transduction pathway
Cell signaling and signal transduction
I. The main idea
A. Cells communicate using extracellular signals
B. Three steps in cell signaling
1. Signal reception
2. Signal transduction
3. Response
C. Types of responses depend on the final effector protein in the pathway
1. Rapid and reversible
a. Allosteric enzyme target metabolic change
b. Cytoskeleton target change in cell shape or motility
c. Transport protein target change in cell or organelle permeability
2. Slower and less reversible:
Transcription regulator target change in gene expression
D. There are a variety of different signal-delivery systems
E. Coordination
1. Same signal, different responses in different cells
2. Same cell, different responses to different combinations of signals
F. Quickly inactivating signaling pathways is as important as turning them on
Fig 16-3 There are a variety of different signal-delivery systems
Multiple signals help
coordinate cell activity
Fig 16-5 Same signal can
lead to different responses in
different cells
Fig 16-6 Same cell can respond
differently to different
combinations of signals
Cell signaling and signal transduction
I. The main idea
A. Cells communicate using extracellular signals
B. Three steps in cell signaling
1. Signal reception
2. Signal transduction
3. Response
C. Types of responses depend on the final effector protein in the pathway
1. Rapid and reversible
a. Allosteric enzyme target metabolic change
b. Cytoskeleton target change in cell shape or motility
c. Transport protein target change in cell or organelle permeability
2. Slower and less reversible:
Transcription regulator target change in gene expression
D. There are a variety of different signal-delivery systems
E. Coordination
1. Same signal, different responses in different cells
2. Same cell, different responses to different combinations of signals
F. Quickly inactivating signaling pathways is as important as turning them on
Cell signaling and signal transduction
I. The main idea
II. Common components of signal transduction pathways
III. Types of signal receptors and their actions
IV. The length of signal transduction pathways depends on the strategy involved
Cell signaling and signal transduction
I. The main idea
II. Common components of signal transduction pathways
A. Second messengers such as:
1. Cyclic nucleotides
2. Calcium ions
3. Inositol triphosphate (IP
3
)
B. Protein kinases
1. Some common PKs
2. Protein kinase cascades
Fig 16-22
Fig 16-20
Fig 16-21
Fig 16-26 Calcium ion
concentration in the
cytosol can increase
rapidly when it is
released from the ER as a
second messenger in
signal transduction
Fig 16-27 Calmodulin--a calcium-binding
protein that mediates the effects of Ca
2+
concentration on calcium-responsive
proteins
Part of Fig 16-25
Inositol triphosphate as
a second messenger
Cell signaling and signal transduction
I. The main idea
II. Common components of signal transduction pathways
A. Second messengers such as:
1. Cyclic nucleotides
2. Calcium ions
3. Inositol triphosphate (IP
3
)
B. Protein kinases
1. Some common PKs
2. Protein kinase cascades
Protein kinase A (PKA) activated by cAMP
Protein kinase C (PKC) activated by calcium
Calmodulin-dependent protein kinase
P
ATP ADP
activator
P
ATP ADP
P
ATP ADP
P
ATP ADP
Inactive
PK1
active
PK1
Inactive
PK3
active
PK3
Inactive
PK3
active
PK3
activation of
effector protein
Cell signaling and signal transduction
I. The main idea
II. Common components of signal transduction pathways
III. Types of signal receptors and their actions
A. A few receptors are intracellular--activated by hydrophobic ligands such as:
1. Steroid hormones
2. Dissolved gases such as nitric oxide (NO)
B. Most receptors are transmembrane proteins with extracellular ligands
1. Ion-channel-coupled receptors
2. G-protein-coupled receptors
a. G proteins and how they work
b. Some targets of activated G proteins
c. Examples of GPCR-initiated pathways
3. Enzyme-coupled receptors
a. Basic action of a receptor tyrosine kinase (RTK)
b. Pathways involving RAS and MAP kinase
c. Pathways involving PI-3 kinase
Fig 16-8 Most signals cannot cross the plasma membrane and
bind to surface receptors, but hydrophobic signals have
intracellular receptors
Fig 16-9
Several hydrophobic
endocrine signals
Fig 16-10
Cortisol binds its receptor in the
cytoplasm and is transported
into the nucleus. Sex steroids
bind nuclear transcription
regulators to activate them.
Figure 16-23 Essential Cell Biology ( Garland Science 2010)
Common components
of signaling pathways
include second
messengers and
protein kinase cascades
(example in Fig 16-23)
Fig 16-11 A&B Nitric oxide is a paracrine
signal involved in blood vessel dilation
Fig 16-11 C Nitric acid often acts
by activating cGMP production
Cell signaling and signal transduction
I. The main idea
II. Common components of signal transduction pathways
III. Types of signal receptors and their actions
A. A few receptors are intracellular--activated by hydrophobic ligands such as:
1. Steroid hormones
2. Dissolved gases such as nitric oxide (NO)
B. Most receptors are transmembrane proteins with extracellular ligands
1. Ion-channel-coupled receptors
2. G-protein-coupled receptors
a. G proteins and how they work
b. Some targets of activated G proteins
c. Examples of GPCR-initiated pathways
3. Enzyme-coupled receptors
a. Basic action of a receptor tyrosine kinase (RTK)
b. Pathways involving RAS and MAP kinase
c. Pathways involving PI-3 kinase
Fig 16-15 There are three
main classes of membrane-
bound receptors
Fig 16-17
G-protein-coupled receptors
activate G proteins by
promoting the exchange of
GTP and GDP
The subunits of the G protein
then usually dissociate
Fig 16-18
Remember: Quickly
inactivating signaling
pathways is as
important as turning
them on
Fig 16-19 In heart muscle, acetylcholine causes the transient
opening of potassium channels via activated subunit of a G protein
Fig 16-24
Activate -subunits of G
proteins often activate
adenylyl cyclase
Then cAMP activates PKA
In many cases (e. g. the
effects of signaling on
hormone production in
endocrine glands and
memory in the brain), PKA
then phosphorylates
transcription regulators
Fig 16-25 Another
common target of G
protein -subunits is
PLC, which then
initiates pathways
involving IP
3
, Ca
2+
and
PKC
Fig 16-23
The action of adenaline on
skeletal muscle cells and liver
cells leading to the rapid
mobilization of glucose was
the first signal transduction
pathway to be completely
understood
Cell signaling and signal transduction
I. The main idea
II. Common components of signal transduction pathways
III. Types of signal receptors and their actions
A. A few receptors are intracellular--activated by hydrophobic ligands such as:
1. Steroid hormones
2. Dissolved gases such as nitric oxide (NO)
B. Most receptors are transmembrane proteins with extracellular ligands
1. Ion-channel-coupled receptors
2. G-protein-coupled receptors
a. G proteins and how they work
b. Some targets of activated G proteins
c. Examples of GPCR-initiated pathways
3. Enzyme-coupled receptors
a. Basic action of a receptor tyrosine kinase (RTK)
b. Pathways involving RAS and MAP kinase
c. Pathways involving PI-3 kinase
Fig 16-30 Basic action of a receptor tyrosine kinase (RTK)
Dimerized receptors
phosphorylate each other
on tyrosine residues
Various adaptor proteins
are then recruited and
activated
Fig 16-31 Often adaptor proteins activate Ras-activating
proteins. Ras is an important integrator of various signals.
It is a small GTPase (remember Ran from Chapter 15?)
Fig 16-32 Ras can initiate
various MAP-kinase cascades
in many cell types.
MAP stands for Mitogen
Activating Protein, but MAP-K
pathways can lead to
differentiation as well as
proliferation
Fig 16-33 A more recently described RTK pathway starts
with PI3-kinase which phosphorylates a membrane lipid
This recruits an adaptor kinase
which is part of the complex
phosphorylation of Akt . . .
Depending on its level of phosphorylation and the position
of the phosphates, Akt is involved in decisions concerning
apoptosis, survival, growth and differentiation
Fig 16-34
Fig 16-35
Cell signaling and signal transduction
I. The main idea
II. Common components of signal transduction pathways
III. Types of signal receptors and their actions
A. A few receptors are intracellular--activated by hydrophobic ligands such as:
1. Steroid hormones
2. Dissolved gases such as nitric oxide (NO)
B. Most receptors are transmembrane proteins with extracellular ligands
1. Ion-channel-coupled receptors
2. G-protein-coupled receptors
a. G proteins and how they work
b. Some targets of activated G proteins
c. Examples of GPCR-initiated pathways
3. Enzyme-coupled receptors
a. Basic action of a receptor tyrosine kinase (RTK)
b. Pathways involving RAS and MAP kinase
c. Pathways involving PI-3 kinase
Cell signaling and signal transduction
I. The main idea
II. Common components of signal transduction pathways
III. Types of signal receptors and their actions
IV. The length of signal transduction pathways differ depending on the strategy
A. Short pathways are a fast track to gene expression
B. Longer pathways allow for more coordination and integration
1. Signal amplifciation
2. Cross-talk between pathways
Some receptors
activate very short
pathways leading to a
fast track to gene
expression
Example in Fig 16-39
dealing with the
hormone prolactin, the
JAK-STAT pathway and
lactation
Fig 16-40 Notch is the receptor for the
contact-dependent signal Delta. When
activated, Notch is itself cleaved to form a
transcription regulator
Cell signaling and signal transduction
I. The main idea
II. Common components of signal transduction pathways
III. Types of signal receptors and their actions
IV. The length of signal transduction pathways differ depending on the strategy
A. Short pathways are a fast track to gene expression
B. Longer pathways allow for more coordination and integration
1. Signal amplifciation
2. Cross-talk between pathways
What is accomplished by
having several steps
between signal reception
and response? - Fig 16-13
Fig 16-29 gives one
example of signal
amplification. Here is
another from a pathway
we have already
discussedadrenaline
(i.e. epinephrine) to
glucose mobilization.
Fig 16-42 - Longer pathways allow for not only signal amplification,
but multiple responses, and cooperative and inhibitory cross-talk
Fig 16-43 Intersecting pathways can integrate multiple incoming
signals
