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

Regulation - cells need to control cellular
processes.
Environmental Stimuli - cells need to be
able to respond to signals from their
environment.

A signal transduction pathway is a series of
steps by which a signal on a cell’s surface is
converted into a specific cellular response
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-2
 factor
Receptor
1
Exchange
of mating
factors

a
a factor
Yeast cell,
mating type a
2
Mating
3
New a/
cell
Yeast cell,
mating type 

a
a/

Pathway similarities suggest that ancestral
signaling molecules evolved in prokaryotes and
were modified later in eukaryotes
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings


In many cases, animal cells communicate using
local regulators, messenger molecules that
travel only short distances
In long-distance signaling, plants and animals
use chemicals called hormones
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
1. Reception - receiving the signal.
2. Transduction - passing on the signal.
3. Response - cellular changes because of the
signal.


The target cell’s detection of a signal coming
from outside the cell.
May occur by:
 Direct Contact
 Through signal molecules



When molecules can flow directly from cell to
cell without crossing membranes.
Plants - plasmodesmata
Animals - gap junctions

May also occur by cell surface molecules that
project from the surface and “touch” another
cell.




The actual chemical signal that travels
from cell to cell.
Often water soluble.
Usually too large to travel through
membranes.
Double reason why they can’t cross cell
membranes.

Behave as “ligands”: a smaller molecule that
binds to a larger one.



Usually made of protein.
Change shape when bind to a signal
molecule.
Transmits information from the exterior to
the interior of a cell.
1. G-Protein linked
2. Tyrosine-Kinase
3. Ion channels
4. Intracellular


Plasma membrane receptor.
Works with “G-protein”, an intracellular
protein with GDP or GTP.



GDP and GTP acts as a switch.
If GDP - inactive
If GTP - active


When active (GTP), the protein binds to
another protein (enzyme) and alters its
activation.
Active state is only temporary.
Fig. 11-7b
Plasma
membrane
G protein-coupled
receptor
Activated
receptor
Inactive
enzyme
Signaling molecule
GDP
CYTOPLASM
GDP
Enzyme
G protein
(inactive)
GTP
2
1
Activated
enzyme
GTP
GDP
Pi
Cellular response
3
4


Very widespread and diverse in functions.
Ex - vision, smell, blood vessel development.


Many diseases work by affecting g-protein
linked receptors.
Ex - whooping cough, botulism, cholera,
some cancers

Up to 60% of all medicines exert their effects
through G-protein linked receptors.


Extends through the cell membrane.
Intracellular part functions as a “kinase”,
which transfers P from ATP to tyrosine on a
substrate protein.
1. Ligand binding - causes two receptor
molecules to aggregate.
2. Activation of Tyrosine-kinase parts in
cytoplasm.
3. Phosphorylation of tyrosines by ATP.
4. After phophorylation, receptor protein fully
activated and is recognized by specific relay
proteins in cell
Fig. 11-7c
Ligand-binding site
Signaling
molecule (ligand)
Signaling
molecule
 Helix
Tyrosines
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosine
kinase proteins
CYTOPLAS
M
Dimer
1
2
Activated relay
proteins
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
P Tyr
P Tyr
6 ATP
Activated tyrosine
kinase regions
6 ADP
P Tyr
Tyr
P Tyr
Tyr
Tyr
P Tyr
P Tyr
Tyr
P
P
Tyr P
P
P
Tyr P
Fully activated receptor
tyrosine kinase
Inactive
relay proteins
3
4
Cellular
response 1
Cellular
response 2

Often activate several different pathways at once,
helping regulate complicated functions such as cell
division.


Protein pores in the membrane that open or
close in response to chemical signals.
Allow or block the flow of ions such as Na+ or
Ca2+.



Activated by a ligand on the extracellular
side.
Causes a change in ion concentration inside
the cell.
Ex - nervous system signals.

Become activated & cause the cellular
response.


Proteins located in the cytoplasm or nucleus
that receive a signal that CAN pass through
the cell membrane.
Ex - steroids (hormones), NO - nitric oxide

Activated protein turns on genes in nucleus.
Fig. 11-8-1
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
DNA
NUCLEUS
CYTOPLASM
Fig. 11-8-2
Hormone
(testosterone)
EXTRACELLULA
R
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
NUCLEUS
CYTOPLASM
Fig. 11-8-3
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
NUCLEUS
CYTOPLASM
Fig. 11-8-4
Hormone
(testosterone)
EXTRACELLULA
R
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
mRNA
NUCLEUS
CYTOPLASM
Fig. 11-8-5
Hormone
(testosterone)
Video clip
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grawhill.com/sites/0072
507470/student_vi
ew0/chapter17/ani
mation__intracellu
lar_receptor_mode
l.html
EXTRACELLULA
R
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
mRNA
NUCLEUS
CYTOPLAS
M
New protein


Often has multiple steps using relay proteins
such as Protein Kinases
Question #9:
 amplification of signal
 provide more opportunities for coordination and
regulation of the cellular response
Protein kinases transfer phosphates
from ATP to protein… phosphorylation
(this activates the protein)
 Protein phosphatases remove the
phosphates from proteins…
dephosphorylation
 Acts as a molecular switch

Fig. 11-9
Signaling molecule
Receptor
Activated relay
molecule
Inactive
protein kinase
1
Active
protein
kinase
1
Inactive
protein kinase
2
ATP
ADP
Pi
P
Active
protein
kinase
2
PP
Inactive
protein kinase
3
ATP
ADP
Pi
Active
protein
kinase
3
PP
Inactive
protein
P
ATP
P
ADP
Pi
PP
Active
protein
Cellular
response


Protein Kinases often work in a cascade with
each being able to activate several molecules.
Result - from one signal, many molecules can
be activated.

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Small water soluble, non-protein molecules
or ions that pass on a signal.
Spread rapidly by diffusion.
Activates relay proteins.
Examples - cAMP, Ca2+
A form of AMP made directly from ATP
by Adenylyl cyclase (enzyme)
 Short lived - converted back to AMP (by
Phosphodiesterase)
 Activates a number of Protein Kinases
which then phosphorylates various
other proteins

Fig. 11-11
First messenger
Adenylyl
cyclase
G protein
G protein-coupled
receptor
GTP
ATP
cAMP
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d_messenger__camp.html
Second
messenger
Protein
kinase A
Cellular responses
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More widely used than cAMP.
Used as a secondary messenger in both Gprotein pathways and tyrosine-kinase
receptor pathways.
Works because of differences in
concentration between extracellular and
intracellular environments. (10,000X)
Involved in muscle cell contraction and cell
division
Fig. 11-12
EXTRACELLULA
R
FLUID
Plasma
membrane
Ca2+ pump
ATP
Mitochondrion
Nucleus
CYTOSOL
Ca2+
pump
Endoplasmic
reticulum (ER)
ATP
Key
High [Ca2+]
Low [Ca2+]
Ca2+
pump
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Secondary messenger attached to
phospholipids of cell membrane.
Sent to Ca channel on the ER.
Allows flood of Ca2+ into the cytoplasm from
the ER, which activate the next protein in
one or more signaling pathways
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#18
Cytoplasmic Regulation
Transcription Regulation in the nucleus (DNA
--> RNA).
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Rearrangement of the cytoskeleton.
Opening or closing of an ion channel.
Alteration of cell metabolism.

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Activating protein synthesis for new
enzymes.
Transcription control factors are often
activated by a Protein Kinase.
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Enzyme cascades amplify the cell’s response
At each step, the number of activated
products is much greater than in the
preceding step
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.swf::Signal%20Amplification
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Different kinds of cells have different
collections of proteins (allows cells to detect
and respond to different signals)
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
-Large relay proteins to which other
relay proteins are attached
-Can increase the signal transduction
efficiency by grouping together
different proteins involved in the same
pathway
Fig. 11-18
Signaling
molecule
Plasma
membrane
Receptor
Three
different
protein
kinases
Scaffolding
protein
Programmed or controlled cell suicide
A cell is chopped and packaged into
vesicles that are digested by scavenger
cells
 Prevents enzymes from leaking out of a
dying cell and damaging neighboring
cells


Fig. 11-19
2 µm
Fig. 11-20
Ced-9
protein (active)
inhibits Ced-4
activity
Mitochondrion
Receptor
for deathsignaling
molecule
Ced-4
Ced-3
Inactive proteins
(a) No death signal
Ced-9
(inactive)
Cell
forms
blebs
Deathsignaling
molecule
Active
Ced-4
Active
Ced-3
Activation
cascade
(b) Death signal
Other
proteases
Nucleases
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Don’t get bogged down in details in this
chapter. Use the KISS principle.
Know :




3 stages of cell signaling
examples of a receptor and how it works
protein kinases and cascades (amplification)
example of a secondary messenger