Cell Signaling

AP Chapter 11

Evolution of cell signaling

Similarities in pathways in bacteria,
protists, fungi, plants, and animals
suggest an early evolution of signaling
pathways
Multicellular better due to coordination
and control of pathways
http://www.youtube.com/watch?v=FsGwgiIv_NU
Boseman video

Bacteria communication
bacteria talking to each other
Quorum sensing- concentration of
signaling molecules allows
bacteria to sense their local density
Ex- Vibrio glowing bacteria
(luciferase enzyme) give off auto
inducers into their environment

autoinducers

Quorum sensing can lead to the

formation of biofilms

Slime molds chemical signaling

Slime molds live as solitary amoebae.
When slime mold cells begin to starve or dehydrate,
they release a pheromone-like chemical called cyclic
AMP. This messenger molecule alerts other slime
mold amoebae. They detect the cAMP and follow the
scent to join forces with the troubled amoebae
forming a large mass of cells.

Other slime mold amoebae detect

the cAMP and follow the scent to
join forces with the troubled
amoebae.

cAMP is an important chemical

word in the language of cells and
seems to be understood and
made by all cells, even our own.

Fruiting body formation in fungi

chemical signaling

Local and long-distance signaling

Direct cytoplasmic connections:
- gap junctions or plasmodesmata in
plant cells
- contact of surface molecules (cell-tocell recognition via receptors

Plasmodesmata in plant cells

Gap junctions in animal cells

Immune cells direct contact

Local regulators nearby cells

paracrine signaling only includes
cells of a particular organ
synaptic signaling between neurons

 Long distance
endocrine signaling
nerve transmission

3 stages of cell signaling

1. Reception
2. Transduction
3. Response

http://www.youtube.com/watch?v=qOVkedxDqQo
Boseman video on cell signaling pathways

Fig. 11-6-1

EXTRACELLULAR
FLUID

1 Reception
Receptor

Signaling
molecule

CYTOPLASM

Plasma membrane

Fig. 11-6-2

CYTOPLASM

EXTRACELLULAR
FLUID

Plasma membrane

1 Reception

2 Transduction

Receptor

Relay molecules in a signal transduction pathway

Signaling
molecule

Fig. 11-6-3

CYTOPLASM

EXTRACELLULAR
FLUID

Plasma membrane

1 Reception

2 Transduction

3 Response

Receptor
Activation
of cellular
response
Relay molecules in a signal transduction pathway

Signaling
molecule

Reception
Ligand the signal molecule, fits like a
lock and key to receptor
Most ligands bind to cell surface
receptors; some bind to intracellular
receptors
Usually induces a shape change in
receptor proteins shape

Types of receptors
Bind with water-soluble molecules on
membrane:
G-Protein-linked Receptor
Tyrosine Kinase Receptor
Ligand-gated Ion Channel
Bind with hydrophobic receptors:
Intracellular Receptors

G- Protein-Linked Receptors
7 protein helices that span the
membrane
Binding of the ligand to the G-protein
receptor, activates a specific G protein
located on the cytoplasm side. How GDP becomes GTP.
The activated G-protein activates a
membrane-bound enzyme which
continues on its pathway.
The GTP goes back to GDP.
Animation: Membrane-Bound Receptors that Activate G
Proteins

Fig. 11-7a

Signaling-molecule binding site

Segment that
interacts with
G proteins
G protein-coupled receptor

Fig. 11-7b

Plasma
membrane

G protein-coupled
receptor

Activated
receptor

Signaling molecule

GDP
CYTOPLASM

GDP

Enzyme

G protein
(inactive)

GTP

1
Activated
enzyme

GTP

GDP
Pi

Cellular response
3

Inactive
enzyme

How important is the G-protein system?

Used by hormones, neurotransmitters,
sensory reception, development.
Many bacteria produce toxins that
interfere with with G-protein systems
Up to 60% of medicines influence Gprotein pathways

Tyrosine kinase receptors

Receptor tyrosine kinases are membrane receptors that attach
phosphates from ATP to tyrosines (Remember kinaseATP.)
Once the receptors are activated, relay proteins bind to them
and become activated themselves.
A receptor tyrosine kinase can trigger multiple signal
transduction pathways at once

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

CYTOPLASM

Dimer

Activated relay
proteins

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

P
P

6 ATP

Activated tyrosine
kinase regions

6 ADP

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

P
P
P

Tyr

Tyr

P
P

Tyr

Tyr

Tyr

Tyr

P
P

Fully activated receptor

tyrosine kinase
Inactive
relay proteins

Cellular
response 1
Cellular
response 2

Tyrosine Kinase Receptors

Binding of the signal molecules

causes the two polypeptides to
join.

They are activated and act as

enzymes to phosphorylate the
tyrosines in the tails.

The receptor protein is now

recognized by relay proteins,
triggering different effects.

Ligand-gated ion channel

A ligand-gated ion channel receptor
acts as a gate
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
Ex- in neurotransmitters and nervous
signal transmission

Fig. 11-7d

1 Signaling
molecule
(ligand)

Gate
closed

Ligand-gated
ion channel receptor
2

Ions

Plasma
membrane

Gate open

Cellular
response

Gate closed

Ligand-Gated Ion Channels

http://msjensen.cehd.umn.edu/1135/Links/Animations/Flash/0003-swf_receptors_link.swf

Intracellular Receptors
Some receptor proteins are intracellular,
found in the cytosol 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
specific genes

Fig. 11-8-5

Hormone
(testosterone)

EXTRACELLULAR
FLUID

Plasma
membrane

Receptor
protein

Hormonereceptor
complex

DNA
mRNA

NUCLEUS

CYTOPLASM

New protein

Intracellular Receptors

http://highered.mcgraw-hill.com/olc/dl/120109/bio46.swf

Signal Transduction
Allow for amplification of signals
Signal coordination and regulation
Involves
1) second messengers (cAMP and Ca +2)
2) relay proteins such as protein
kinases

How does epinephrine work?...an

example of cAMP messenging

Epinephrine acts via cyclic AMP (cAMP) as

a second messenger.

An activated G protein activates the

enzyme adenylyl cyclase (THINK CYCLING!)
which turns ATP to cAMP.

Then cAMP can activate other inactive

molecules to reach the desired product.
action of epinephrine Video | DnaTube.com - Scientific Video Site

Fig. 11-10

Adenylyl cyclase

Phosphodiesterase

Pyrophosphate
P
ATP

Pi
cAMP

AMP

Fig. 11-11

First messenger

Adenylyl
cyclase

G protein

G protein-coupled
receptor

GTP
ATP
cAMP

Second
messenger
Protein
kinase A

Cellular responses

cAMP second messenger

systems

Membrane Structure

 Calcium ions also act as second

messengers.
One example is activating an enzyme
phospholipase C to produce two more
messengers which will open Ca channels.
The signal receptor may be a G protein or a
tyrosine kinase receptor.

Fig. 11-13-3

EXTRACELLULAR
FLUID

Signaling molecule
(first messenger)
G protein
DAG
GTP

G protein-coupled
receptor

PIP2

Phospholipase C

IP3
(second messenger)

IP3-gated
calcium channel

Endoplasmic
reticulum (ER)

CYTOSOL

Ca

Various
proteins
activated

2+

Ca2+
(second
messenger
)

Cellular
responses

RELAY PROTEINS
Enzymes called protein kinases are also
important links in transduction.
A protein kinase catalyzes the transfer of
PHOSPHATE GROUPS from ATP to another
protein to activate it.
Amplification is possible in these type of
pathways.

Fig. 11-9

Signaling molecule

Receptor

Activated relay
molecule

Inactive
protein kinase
1

ATP

Inactive
protein kinase
3

e
ad
sc

PP

ca

Pi

Active
protein
kinase
2

n
io

ADP

t
yla

Inactive
protein kinase
2

or
ph
os
Ph

Active
protein
kinase
1

ATP
ADP

Pi

Active
protein
kinase
3

PP
Inactive
protein

ATP

ADP

Pi

PP

Active
protein

Cellular
response

This can get pretty complicated!

Cell Responses
Alteration of metabolism
Rearrangement of cytoskeleton
Modulation of gene activity

Fig. 11-14

Growth factor

Reception

Receptor

Phosphorylation
cascade

Modulating
Gene
Activity

Transduction

CYTOPLASM

Inactive
transcription
factor

Active
transcription
factor
P

Response

DNA
Gene
NUCLEUS

mRNA

Fig. 11-15

Reception
Binding of epinephrine to G protein-coupled receptor (1 molecule)

Transduction
Inactive G protein
Active G protein (102 molecules)

Alteration of
Metabolism

Inactive adenylyl cyclase

Active adenylyl cyclase (10 2)
ATP
Cyclic AMP (104)
Inactive protein kinase A
Active protein kinase A (104)
Inactive phosphorylase kinase
Active phosphorylase kinase (10 5)
Inactive glycogen phosphorylase
Active glycogen phosphorylase (10 6)
Response

Glycogen
Glucose-1-phosphate
(108 molecules)

Fig. 11-16

RESULTS

Rearrangement
Wild-type (shmoos)
Of cytoskeleton

Fus3

formin

CONCLUSION
1

Mating
factor G protein-coupled
receptor

Shmoo projection
forming
Formin
P
Fus3

GDP

GTP
Phosphorylation
cascade

Actin
subunit

P
Formin

Formin
P

Fus3

Fus3
P

Microfilament
5

Fine-Tuning of the Response

Multistep pathways have two important benefits:
Amplifying the signal (and thus the response)
Contributing to the specificity of the response

Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

The Specificity of Cell Signaling and

Coordination of the Response
Different kinds of cells have different
collections of proteins which allow cells
to detect and respond to different
signals.
Even the same signal can have different
effects in cells with different proteins
and pathways

Fig. 11-17

Same signal
- different
effects in
cells with
different
proteins and
pathways

Pathway
branching and
cross-talk
further help the
cell coordinate
incoming
signals

Signaling
molecule

Receptor

Relay
molecule
s

Response 1
Cell A. Pathway leads
to a single response.

Response 2

Response 3

Cell B. Pathway branches,

leading to two responses.

Activation
or inhibition

Response 4
Cell C. Cross-talk occurs
between two pathways.

Response 5
Cell D. Different receptor
leads to a different response.

Signaling Efficiency: Scaffolding Proteins

and Signaling Complexes
Scaffolding proteins are large relay proteins to
which other relay proteins are attached
Scaffolding proteins can increase the signal
transduction efficiency by grouping together
different proteins involved in the same pathway

Fig. 11-18

Signaling
molecule

Plasma
membrane

Receptor

Scaffolding
protein

Three
different
protein
kinases

Disruptions in cell signaling

pathways
Bacterial infections (cholera, anthrax,
pertussis)
Animal toxins
Hormone imbalances (diabetes)
Cancer
Plant diseases
Boseman video on disruptions

Apoptosis (programmed cell death) integrates

multiple cell-signaling pathways
Apoptosis is programmed or controlled cell suicide
A cell is chopped and packaged into vesicles that
are digested by scavenger cells
Apoptosis prevents enzymes from leaking out of a
dying cell and damaging neighboring cells
Apoptosis is important in shaping an organism
during embryonic development

Fig. 11-20b

Ced-9
(inactive)

Cell
forms
blebs

Deathsignaling
molecule

Active Active
Ced-4 Ced-3

Activation
cascade

(b) Death signal

Other
proteases
Nucleases

Apoptotic Pathways and the Signals That

Trigger Them
Caspases are the main proteases
(enzymes that cut up proteins) that carry
out apoptosis
Apoptosis can be triggered by:
An extracellular death-signaling ligand
DNA damage in the nucleus
Protein misfolding in the endoplasmic
reticulum

Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Apoptosis evolved early in animal

evolution and is essential for the
development and maintenance of all
animals
Apoptosis may be involved in some
diseases (for example, Parkinsons and
Alzheimers); interference with apoptosis
may contribute to some cancers

Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 11-21

Interdigital tissue

1 mm