Lecture 7 – Cell Communication
ch15
BIOL211 Spring 2012
1
Previously we talked about channel proteins,
membrane-bound proteins, protein
structure, and ATP. This is where all that
starts to come together…
BIOL211 Spring 2012
2
In this lecture
•
•
•
•
Types of cell signaling
“Conformational change” in proteins
Stages in cell signal reception
Membrane-bound cell signaling
– GPCRs
– RTKs
– Ion channels
• Non-membrane bound signaling
• Signal transduction cascades
• Second messengers
– cAMP
– IP3, Ca2++
• Regulating cell signaling
BIOL211 Spring 2012
3
How do cells talk to each other?
• Cell-to-cell communication is essential for both
multicellular and unicellular organisms
• Biologists have discovered some universal
mechanisms of cellular regulation
• Cells most often communicate with each other via
chemical signals
• For example, the fight-or-flight response is
triggered by a signaling molecule called
epinephrine
BIOL211 Spring 2012
4
BIOL211 Spring 2012
5
Problem: signals must travel from the outside
of the cell into the interior
The plasma membrane is selectively permeable, and contains embedded proteins
One of the functions of these proteins is to act as signaling molecules
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
Two types of signals: those that go through membrane receptors, and
those that go inside the cell to intercellular receptors
BIOL211 Spring 2012
6
BIOL211 Spring 2012
7
What are signals made of ?
• Signaling chemicals can either be small
organic molecules or proteins
Epinephrine (AKA adrenaline)
Stimulates fight or flight response
BIOL211 Spring 2012
GH – Growth hormone
Stimulates growth and replication
in cells
BST is a GH in cows
8
What sorts of things do signals
signal?
•
•
•
•
•
Cell growth and division
Embryonic development
Fat storage and breakdown
Carbohydrate storage and breakdown
Innumerable other things
BIOL211 Spring 2012
9
BIOL211 Spring 2012
10
Types of cell signaling
• Local (AKA paracrine signaling)
– Direct contact through cell-cell
junctions or cell-cell recognition
– Heart cells, nerve cells
• Long-distance (exocrine signaling)
– Secretion of chemical
messengers called hormones
– Testes and ovaries, pituitary gland
Through
exocytosis!!
The ability of a cell to respond to a signal
depends on whether or not it has a receptor
specific to that signal
BIOL211 Spring 2012
11
BIOL211 Spring 2012
12
How do signals interact with the cell?
• A signal is secreted, either locally or long-distance
• Membrane proteins on target cells recognize a signal
– “Lock and key” again
– The binding between a signal molecule (ligand) and
the membrane protein (receptor) is highly specific
BIOL211 Spring 2012
13
“Conformational Change”
• Ligand binding triggers a conformational change
in the receptor
– Proteins are flexible in their backbones
– Adding on some atoms in a particular location on
the protein will change hydrogen bonding and
Van der Waals patterns
BIOL211 Spring 2012
14
More examples of conformational
changes
What is the ligand here?
BIOL211 Spring 2012
15
Transmembrane proteins and
conformational change
• A ligand binds to the extracellular (outside) face, and
changes the shape of the entire protein
– The intercellular portion now has a different shape
– That different shape can now bind different things
Ligand binds here
Ribose binds outside and
causes the this transmembrane
protein to change shape. Once
it has, the inside portion can
now bind ATP
ATP binds here
BIOL211 Spring 2012
16
Stages of signal reception
• Cells receiving signals go through three
stages:
– Reception
– Transduction
– Response
BIOL211 Spring 2012
17
Figure 11.6-1
EXTRACELLULAR
FLUID
CYTOPLASM
Plasma membrane
1 Reception
Receptor
Signaling
molecule
BIOL211 Spring 2012
18
Figure 11.6-2
EXTRACELLULAR
FLUID
1 Reception
CYTOPLASM
Plasma membrane
2 Transduction
Receptor
Relay molecules in a signal transduction
pathway
Signaling
molecule
BIOL211 Spring 2012
19
Figure 11.6-3
EXTRACELLULAR
FLUID
1 Reception
CYTOPLASM
Plasma membrane
2 Transduction
3 Response
Receptor
Relay molecules in a signal transduction
pathway
Activation
of cellular
response
Signaling
molecule
BIOL211 Spring 2012
20
Types of membrane receptors
• Water-soluble signals cannot travel through
the cell membrane and so rely on membrane
receptors to pass along their signal
• There are four main types of membrane
receptors:
–
–
–
–
G protein-coupled receptors
Receptor tyrosine kinases
Ion channel receptors
Enzyme receptors
BIOL211 Spring 2012
21
G-protein Coupled Membrane Receptors
• The largest family of cell-surface receptors (>1000
different members)
• A GPCR is a plasma membrane receptor that works with
the help of a G protein
– A specific portion of its intercellular portion is
dedicated to binding G protein
• The G protein is an
on/off switch
– G protein itself has a ligand
called GDP (guanosine
diphosphate)
– If GDP is bound to the G
protein, the G protein
is inactive
BIOL211 Spring 2012
22
Signaling
molecule =
ligand
BIOL211 Spring 2012
23
How it works: GPCRs
• A ligand binds the outside face of GPCR
• The inside face of GPCR changes, allowing G
protein to bind
• GDP is phosphorylated into GTP, causing G
protein to detach from GPCR
– Phosphorylation: adding a phosphate group
• G protein with its new GTP can now go activate
other cellular enzymes
– It does this by hydrolyzing its phosphate
group transforming GTP back into GDP
BIOL211 Spring 2012
24
GTP vs. ATP and phosphorylation
• Both used to power cellular activity
• Phosphate is a highly electronegative group,
and bends protein backbones around it
• Adding a phosphate group (phosphorylating) to
any part of a protein will likely change its
structure
• Some enzymes like to use ATP, some like GTP
ATP
BIOL211 Spring 2012
GTP
25
Hydrolysis of ATP and GTP
• So, breaking a phosphate off (hydrolyzing) ATP not only
releases lots of energy…
• But that phosphate group can also be attached to a
Hydrolyzing =
protein, causing its shape to change
breaking apart
using water
• Changing its shape = changing its function
• A protein that previously did not bind with anything can
be “activated” by adding a phosphate group
This is the
phosphate group
that’s transferred to
proteins
This also applies to GTP
BIOL211 Spring 2012
26
GPCRs: A Summary
The players:
•
•
•
•
•
•
GPCR: G-protein coupled receptor
Ligand
G protein
GTP
Phosphate group
cAMP (second messenger, explained in slide 50)
The processes:
• Phosphorylation
• Hydrolysis
BIOL211 Spring 2012
27
Receptor Tyrosine Kinases
• RTKs work by attaching phosphates to
tyrosine residues
– These residues are on the intercellular
(inside) portion of the protein
– Tyrosine is a large, polar amino acid
– A residue is one amino acid singled out in a
polypeptide chain
BIOL211 Spring 2012
28
Figure 11.7c
Signaling
Ligand-binding site
molecule (ligand)
Signaling
molecule
 helix in the
membrane
Tyrosines
CYTOPLASM
1
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosine
kinase proteins
(inactive monomers)
Dimer
2
Activated relay
proteins
3
Tyr
Tyr
P Tyr
Tyr P
Tyr
Tyr
P Tyr
Tyr P
Tyr
Tyr
P Tyr
Tyr P
6 ATP
Activated tyrosine
kinase regions
(unphosphorylated
dimer)
6 ADP
Fully activated
receptor tyrosine
kinase
(phosphorylated
dimer)
4
BIOL211 Spring 2012
P Tyr
Tyr P
P Tyr
Tyr P
P Tyr
Tyr P
Cellular
response 1
Cellular
response 2
Inactive
relay proteins
29
How it works: RTKs
• Ligand binds to the receptor tyrosine kinase
• Two adjacent RTKs “dimerize”
– They come together to form one giant transmembrane protein
– A dimer is a protein with two of the same subunits (remember
quaternary protein structure??)
• The new dimer shape allows the phosphorylation of
the tyrosines
– One phosphate group is popped off ATP and transferred to one
tyrosine
• The tyrosine residue + phosphate can now activate
other enzymes (called relay proteins in the picture)
BIOL211 Spring 2012
30
BIOL211 Spring 2012
31
Ion Channel Receptors
• These can be the same channels that help
with active diffusion
• Acts as gates letting ions flow through
when activated
• When a ligand binds the ion channel
receptor, it opens to allow ions like Na+ or
Ca2+
• Specific ion channels allow in specific ions
– A sodium ion channel won’t let in calcium ions
BIOL211 Spring 2012
32
Ion Channel Receptors
Yeah, this one is really this simple
BIOL211 Spring 2012
33
GABA and Ion Channel Receptors
• GABA is a neurotransmitter
• When it binds to an ion channel in the cell
membrane of a nerve cell, it opens it
• This allows the flow of chloride ions into the cell,
which helps neurons communicate with each
other
BIOL211 Spring 2012
34
Enzyme-coupled receptors
• An enzyme-coupled receptor will activate
an enzyme on the interior of the cell when
a ligand is bound
BIOL211 Spring 2012
35
Refining our idea of signal
transduction
Receptor Tyrosine Kinase
Or
G-protein coupled receptor
BIOL211 Spring 2012
This isn’t a strictly accurate
picture of ion channels, but they
do go through transduction and
response
36
If you are reviewing this at
home…take a break!
And watch a cool fiddling video
Warning: loud music (duh)
BIOL211 Spring 2012
37
What happens when the signal molecule
is able to travel through the plasma
membrane?
Small or hydrophobic chemical messengers can
readily cross the membrane
Examples of hydrophobic messengers are the steroid and thyroid
hormones of animals
Intracellular receptor proteins, not
membrane proteins, are the signal
receptors in this case
Intracellular receptor proteins are found floating in the cytoplasm or nucleus
BIOL211 Spring 2012
38
Figure 11.9-1
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
DNA
NUCLEUS
CYTOPLASM
BIOL211 Spring 2012
39
Figure 11.9-2
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
NUCLEUS
CYTOPLASM
BIOL211 Spring 2012
40
Figure 11.9-3
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
Once activated, the
hormone-receptor
complex can now
travel through the
nuclear pores into
the membrane
DNA
NUCLEUS
CYTOPLASM
BIOL211 Spring 2012
41
Figure 11.9-4
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
“Cellular
response” in
other pictures
This entire process
is called signal
transduction
DNA
mRNA
NUCLEUS
CYTOPLASM
BIOL211 Spring 2012
42
Summary of Signal Receptors
• Membrane receptors
– Used for signaling molecules that can’t travel
inside the membrane
– Three main types: GPCRs, RTKs, ion-gated
channels
• Intracellular receptors
– Used for signaling molecules that can travel
through the membrane
BIOL211 Spring 2012
43
The role of protein phosphorylation in
signal transduction cascades
Fischer and Krebs
won the 1992 Nobel
prize for discovering
protein
phosphorylation
• Phosphorylating a protein will turn it form its
“inactive” form to its “active” form
– Phosphorylation: the transfer of a phosphate
group from ATP/GTP to a protein
• The kinases are enzymes responsible for
phosphorylation
• The phosphatases are enzymes that remove
phosphate groups added on by kinases
BIOL211 Spring 2012
44
Signal Transduction Cascades
• The molecules that relay a signal from
receptor to response are mostly proteins
• Like falling dominoes, the 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, usually a shape change in a
protein
BIOL211 Spring 2012
45
Figure 11.10
Signaling molecule
This can be
a G protein
Receptor
Activated relay
molecule
Inactive
protein kinase
1
Active
protein
kinase
1
Inactive
protein kinase
2
The relay molecule
activates protein
kinase 1
The newly
activated protein
kinase 1 activates
protein kinase 2
through
phosphorylation
Pi
ATP
ADP
P
Active
protein
kinase
2
PP
Inactive
protein kinase
3
Pi
ATP
ADP
Active
protein
kinase
3
PP
Inactive
protein
P
ATP
P
ADP
Pi
BIOL211 Spring 2012
PP
Active
protein
Cellular
response
46
Phosphorylation cascades: How they work
Step 1: Ligand binds to the receptor
Step 2: Receptor activates a relay molecule
This can be through a G protein, a protein activated by an RTK, or
another signaling mechanism*
Step 3: Relay molecule activates a protein kinase
Step 4: That protein kinase activates another protein kinase.
There may be two to dozens of kinases activating each other before the
cascade gets to the end
Step 5: The final protein kinase activates the target protein
Step 6: The target protein does its ‘job’
Step 7: The cellular response takes place
Phosphorylation cascades
can follow GPCRs, RTKs,
or ion channels
BIOL211 Spring 2012
*Remember, GPCRs, RTKs,
and ion channels are just the
three common signaling
mechanisms, not the only ones
47
Figure 11.6-3
This is where the phosphorylation
cascade takes place
1 Reception
2 Transduction
Relay molecules in a signal transduction
pathway
BIOL211 Spring 2012
3 Response
Activation
of cellular
response
48
What is a “cellular response”?
• Ultimately, a signal transduction pathway leads to
regulation of one or more cellular activities
• The response may occur in the cytoplasm or in the
nucleus
• 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,
regulating what genes are expressed where
BIOL211 Spring 2012
49
Why study all this nonsense?
• RTKs and GPCRs provide common patterns
of protein-protein interaction you will see
over and over again
• RTK signaling gone wrong is a commonly
found in cancers
• Many drugs depend on disrupting these
RTKs, GPCRs, and ion channels receptors to
have their effect
BIOL211 Spring 2012
50
What signaling pathways look like in the “big
leagues”
Learning
these basic
patterns
prepare you
for this stuff
later on
(It’s like practicing
chords and scales
when learning an
instrument –
learning the
underlying structure
of music helps you
more easily learn
actual songs)
BIOL211 Spring 2012
51
Let’s refine our signal transduction model a
little more
G Protein*
1 Reception
2 Transduction
3 Response
Activation
of cellular
response
Receptor
Tyrosine Kinase
Or
G-protein
coupled receptor
The phosphorylation cascade
*In the cases where GPCR is used as the receptor
BIOL211 Spring 2012
52
Let’s add in something called “second
messengers”
Second
messengers
1 Reception
G Protein*
2 Transduction
3 Response
Activation
of cellular
response
Receptor
Tyrosine Kinase
Or
G-protein
coupled receptor
The phosphorylation cascade
*In the cases where GPCR is used as the receptor
BIOL211 Spring 2012
53
What are second messengers?
• Second messengers are molecules or
ions that spread throughout a cell by
diffusion
– Small, water-soluble, non-protein
• Second messengers participate in
pathways initiated by GPCRs and RTKs
• Second messengers also diffuse through
gap junctions, allowing signals to rapidly
spread through adjacent cells
BIOL211 Spring 2012
54
What do second messengers look like?
Cyclic AMP (cAMP), calcium ions, inositol triphosphate (IP3),
diacylglycerol (DAG), and nitrous oxide (NO) are common
second messengers
Inositol triphosphate
cAMP
Diacylglycerol
cAMP forms from ATP
BIOL211 Spring 2012
55
cAMP as a second messenger
• Formation of cAMP is an important part of
GPCR signal transduction
• Many signal molecules (ligands) trigger
formation of cAMP
• cAMP is the link between the G protein
and the first protein in the
phosphorylation cascade
• cAMP is produced by adenylyl cyclase + G
protein
BIOL211 Spring 2012
56
Ligand
First messenger
G protein
G protein-coupled
receptor
Adenylyl
cyclase
GTP
ATP
Second
cAMP messenger
Protein
kinase A
Cellular responses
BIOL211 Spring 2012
57
Refining our model: how GPCRs work
• A ligand binds the outside face of GPCR
• The inside face of GPCR changes, allowing G
protein to bind
• GDP is phosphorylated into GTP, causing G
protein to detach from GPCR
• G protein with its new GTP can now go activate
adenylyl cyclase
• Adenylyl cyclase converts AMP to cAMP
• cAMP activates protein kinases in the
phosphorylation cascade
BIOL211 Spring 2012
58
Calcium ions as a second messenger
• Calcium ions (Ca2+) act as a second messenger in
many pathways – including GPCRs and RTKs
• Calcium second messengers are involved in
muscle cell contractions, cell division and in
plants, greening in response to light
• Pathways leading to the release of calcium
involve inositol triphosphate (IP3) and
diacylglycerol (DAG) as additional second
messengers
BIOL211 Spring 2012
59
If you are reviewing this at home…STOP
Take another break!
And look at this cute picture of dogs enjoying a snow day
BIOL211 Spring 2012
60
Regulating cell signaling
• A stoplight has to have both a red and
green light, right? Same with cell signaling
• Signaling molecules can not only start and
stop a signal transduction pathway, but
also increase or decrease its strength
Think of a
dimmer switch
rather than an
on/off switch
BIOL211 Spring 2012
61
Regulating GPCRs
• GPCR signals can be regulated by other proteins
• These proteins inactivate adenylyl cyclase,
preventing cAMP
formation
– Even if a signal is sent
to the GPCR, nothing
will happen since
cAMP is not formed
Any point of
the signal
cascade can be
inhibited
BIOL211 Spring 2012
62
• There is a ‘timer’ on G-proteins
– GTP bound to G-protein is unstable and will
spontaneously hydrolyze to GDP after a
certain amount of time
– This inactivates the G-protein
• cAMP is rapidly broken down by other
enzymes and so has a limited shelf-life as
well
– This means cAMP’s effects are short-lived
unless it is continuously produced
BIOL211 Spring 2012
63
Cholera and G-protein regulation
• The bacteria responsible for cholera secretes
the cholera toxin into nearby intestinal cells
• The cholera toxin modifies the G protein so it
is unable to hydrolyze GTP to GDP
– The G protein is constantly active
– Constantly active = constant cAMP production
• High cAMP levels in intestinal cells causes
them to expel a lot of water and salt
• Diarrhea and death ensues
BIOL211 Spring 2012
64
“Heart medication” and cAMP
regulation
• cAMP also causes the smooth muscle cells
in arteries to relax
• A compound that inhibits hydrolysis of
cAMP back to AMP prolongs the arteryrelaxation signal and promotes blood flow
• Originally used as a heart medication
• Now…?
BIOL211 Spring 2012
65
Viagra
inhibits
cAMP being
converted
back to ATP
Cholera toxin
inhibits GTP going
back to GDP
BIOL211 Spring 2012
66
Fine-tuning the signal response
• There are three aspects of fine-tuning to
consider
– Amplifying the signal (and thus the
response)
– Specificity of the response
– Termination of the signal
BIOL211 Spring 2012
67
Signal Amplification
• Phosphorylation cascades amplify the cell’s
response
• At each step, the number of activated products is
much greater than in the preceding step
• The end result: one ligand binding can have a
huge, cell-wide effect
– Of course, inhibitory molecules can cancel out all or
some of this amplification
Enzymes – including kinases in
phosphorylation cascades – are not
used up in a biochemical reactions and
so can make lots of product protein with
very little time and energy investment
BIOL211 Spring 2012
68
Each new step
of the
phosphorylation
cascade
increases the
protein levels in
the next step
If even one of
these proteins
is ineffective or
damaged…what
happens?
BIOL211 Spring 2012
69
Specificity of the response
• Different cells will have different responses
to the same signal
– This is because different cells have different
collections of proteins
A heart cell will
respond to epinephrine
by contracting faster
A liver cell will respond
to epinephrine by
breaking down glycogen
into glucose for quick
energy
BIOL211 Spring 2012
70
Figure 11.18
And of course, there are different types of responses within the same cell
Signaling
molecule
Receptor
Relay
molecules
Response 1
Cell A. Pathway leads
to a single response.
Activation
or inhibition
Response 2
Response 3
Response 4
Cell B. Pathway branches, Cell C. Cross-talk occurs
leading to two responses. between two pathways.
BIOL211 Spring 2012
Response 5
Cell D. Different receptor
leads to a different
response.
71
Termination of the signal
• Inactivation mechanisms are an essential
aspect of cell signaling
– What happens if you get a neverending signal
for cell division?
• If ligand concentration falls, fewer
receptors will be bound
• Unbound receptors revert to an inactive
state
BIOL211 Spring 2012
72
G-proteins and cancer
• Ras is a type of G protein
• It is a major culprit in cancer – malfunctioning
Ras is present in 25% of all tumors and 90% of
all malignant tumors
• When switched on, Ras controls cell growth,
differentiation, and survival
– Ras is switched on when it is bound to GTP
• A single-nucleotide mutation in the Ras gene
causes it to hold on to GTP
– Continually stimulates cell growth - cancer
BIOL211 Spring 2012
73
RTKs and cancer
• VEGF (vascular endothelial growth factor)
is an RTK that stimulates angiogenesis
• Cancer cells need large supplies of oxygen
and nutrients to grow
• Cancer cells trigger angiogenesis to supply
themselves with these nutrients
BIOL211 Spring 2012
74
RTKs and cancer
• Avastin is a drug that mimics the natural ligand
of VEGF
• When administered, Avastin halts angiogenesis
– Body needs angiogenesis to repair wounds
– Decreased rate of wound healing and hypertension
are common side effects
– Extends life on average ~5 months at the cost of
$50,000
BIOL211 Spring 2012
75
It doesn’t end there…
• These are just some of the important types
of signaling pathways
• There are LOTS of others
–
–
–
–
–
MAP-KKK pathway
PI3K/AKT pathway
Notch-mediated juxtracrine signaling
Cytokine signaling pathway
Etc…
Let’s actually apply this stuff and look at a signaling pathway
BIOL211 Spring 2012
76
Epinephrine
• AKA adrenaline, responsible for the ‘fight
or flight’ response
• Causes:
– Constricted arteries for increased blood flow
– Heart to beat faster
– Glycogen to break down into glucose for quick
energy
– Thickened secretions of salivary glands,
causing dry mouth
– Opens airways for increased oxygen intake
BIOL211 Spring 2012
77
• Step 1: Epinephrine is released by the
adrenal gland in response to a stimulus
Such as a bear
• Step 2: Epinephrine then travels through
the bloodstream (this is long-distance signaling)
• Step 3: Epinephrine finds and attaches to
a GPCR called β-adrenergic receptor
BIOL211 Spring 2012
78
• Step 4: The β-adrenergic receptor activates a G
protein
• Step 5: The G protein’s GDP is phosphorylated
into GTP
• Step 6: G protein detaches from the β-adrenergic
receptor and attaches to adenylyl cyclase,
activating it
• Step 7: Adenylyl cyclase begins creating cAMP
from ATP
BIOL211 Spring 2012
79
• Step 8: cAMP activates the first protein kinase
• Step 9: The phosphorylation cascade takes place,
with the number of proteins at each step
increasing exponentially
• Step 10: In liver cells, protein kinases activate
glycogen phosphorylase
– Step 10a: In heart cells, protein kinases causes actin
and myosin filaments to contract
• Step 11: Glycogen phosphorylase converts glycogen
into glucose
– Step 11a: Heart muscle cell contracts
BIOL211 Spring 2012
80
• Step 12: Epinephrine only temporarily
binds to the β-adrenergic receptor. As
soon as it dissociates, cAMP is no longer
produced
• Step 13: The phosphorylation cascade
quiets
• Step 14: Blood vessels relax, heart slows
down, glycogen production resumes, etc.
BIOL211 Spring 2012
81
BIOL211 Spring 2012
82
Epinephrine in medicine
• “Epi pens” containing epinephrine are carried
around by people who have life-threatening
allergic reactions
• Allergic reactions causes the throat to swell and
cuts off the airway
• Epinephrine opens airways
• Also useful in heart attacks to stimulate a
heartbeat
BIOL211 Spring 2012
83
We’re done!
BIOL211 Spring 2012
84
Recommended videos
• Cold Springs Harbor – Cell Signals (VERY good
and highly recommended, but long)
– http://www.youtube.com/watch?v=89W6uACEb7M
• GPCR animation (with bonus Pachelbel Canon in D)
– http://www.youtube.com/watch?v=FtVb7r8aHco
• cAMP signaling
– http://www.youtube.com/watch?v=0nA2xhNiAow&feature=related
• Self-quiz (lots of these look like good test questions…)
– http://www.biology.arizona.edu/cell_bio/problem_sets/signaling/Index.html
Ignore questions 5, 10, and 12
If you find any others you like, shoot me an e-mail and I’ll post ‘em on the website!
BIOL211 Spring 2012
85
Questions?
E-mail me: [email protected]
Call me: (818) 321-2490
Skype me: liz.thomas306
The smallest known
species of frog, recently
discovered!
BIOL211 Spring 2012
86