1. Signal Transduction Pathways
Cell Communication
Signal Transduction Pathways

2. Local Signaling
Cells in a multicellular organism communicate by chemical messengers
Animal and plant cells have cell junctions that directly connect the cytoplasm of adjacent cells
In local signaling, animal cells may communicate by direct contact, or cell-cell recognition
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3. Gap junctions between animal cells Plasmodesmata between plant cells
Fig. 11-4
Plasma membranes
Gap junctions
between animal cells
Plasmodesmata
between plant cells
(a) Cell junctions
Figure 11.4 Communication by direct contact between cells
(b) Cell-cell recognition

4. (a) Paracrine signaling (b) Synaptic signaling
Fig. 11-5ab
Local signaling
Target cell
Electrical signal
along nerve cell
triggers release of
neurotransmitter
Neurotransmitter
diffuses across
synapse
Secreting
cell
Secretory
vesicle
Figure 11.5 Local and long-distance cell communication in animals
Local regulator
diffuses through
extracellular fluid
Target cell
is stimulated
(a) Paracrine signaling
(b) Synaptic signaling

5. Long-distance signaling
In long-distance signaling, animals and plants use chemical messengers called hormones.
Hormones are chemicals made in one area of the body that are delivered to other areas.

6. Long-distance signaling
Fig. 11-5c
Long-distance signaling
Endocrine cell
Blood
vessel
Hormone travels
in bloodstream
to target cells
Figure 11.5 Local and long-distance cell communication in animals
Target
cell
(c) Hormonal signaling

7. What are Signal transduction pathways?
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.
In general there are 3 steps:
1) Reception
2) Transduction
3) Response

8. Plasma membrane 1 Reception Receptor Signaling molecule 1
Fig
EXTRACELLULAR
FLUID
CYTOPLASM
Plasma membrane 1 1
Reception
Receptor
Figure 11.6 Overview of cell signaling
Signaling
molecule

9. Plasma membrane 1 Reception Transduction Receptor Signaling molecule 1
Fig
EXTRACELLULAR
FLUID
CYTOPLASM
Plasma membrane 1 1
Reception 2
Transduction
Receptor
Relay molecules in a signal transduction pathway
Figure 11.6 Overview of cell signaling
Signaling
molecule

10. Plasma membrane 1 Reception Transduction Response Receptor Activation
Fig
EXTRACELLULAR
FLUID
CYTOPLASM
Plasma membrane 1
Reception 2
Transduction 3
Response
Receptor
Activation
of cellular
response
Relay molecules in a signal transduction pathway
Figure 11.6 Overview of cell signaling
Signaling
molecule

11. Step 1: reception
In Step 1, Reception: a signaling molecule binds to a receptor protein, causing it to change shape.
Ligand: the signaling molecule
Receptor: a molecule (usually a protein) on the surface of a cell that recognizes and binds to a ligand
The binding between a ligand and its’ receptor is highly specific.

12. Receptors in the Plasma Membrane
Most water-soluble signal molecules bind to specific sites on receptor proteins in the plasma membrane
Examples of membrane receptors:
G protein-coupled receptors
Ion channel receptors
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13. G-Protein-Coupled Receptors
A G protein-coupled receptor is a plasma membrane receptor that works with the help of a G protein
The G protein acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

14. Fig. 11-7b Plasma membrane G protein-coupled receptor Inactive enzyme
Activated
receptor
Signaling molecule
GDP
G protein
(inactive)
Enzyme
GDP
GTP
CYTOPLASM 1 2
Activated
enzyme
Figure 11.7 Membrane receptors—G protein-coupled receptors, part 2
GTP
GDP P i
Cellular response 3 4

15. Ligand-gated Ion Channel Receptor
A ligand-gated ion channel receptor acts as a gate 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

16. 1 Signaling molecule (ligand) Gate closed Ions Plasma membrane
Fig. 11-7d 1
Signaling
molecule
(ligand)
Gate
closed
Ions
Plasma
membrane
Ligand-gated
ion channel receptor 2
Gate open
Cellular
response
Figure 11.7 Membrane receptors—ion channel receptors 3
Gate closed

17. Step 2: Transduction
In Step 2, Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell
Transduction: the conversion of a signal outside the cell to a form that can bring about a specific cellular response.

18. Signal Transduction Pathways
Signal transduction usually involves multiple steps, called a signal cascade.
Multi-step pathways (signaling cascades) can amplify a signal; even just a few molecules can cause a large cell response.
Advantage: multi-step pathways can provide for more ways to coordinate and regulate the response.
Multi-step pathways also allow for more specificity in the response.

19. Phosphorylation cascade
Fig. 11-9
Signaling molecule
Receptor
Activated relay
molecule
Inactive
protein kinase 1
Active
protein
kinase 1
Inactive
protein kinase 2
ATP
Phosphorylation cascade
ADP
Active
protein
kinase 2 P PP P i
Figure 11.9 A phosphorylation cascade
Inactive
protein kinase 3
ATP
ADP
Active
protein
kinase 3 P PP P i
Inactive
protein
ATP
ADP P
Active
protein
Cellular
response PP P i

20. Second Messengers
The extracellular signal molecule that binds to the receptor is a pathway’s “first messenger”
Second messengers are small, non-protein, water-soluble molecules or ions that spread throughout a cell by diffusion
Second messengers participate in pathways initiated by G protein-coupled receptors
Cyclic AMP and calcium ions are common second messengers
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21. Cyclic AMP
Cyclic AMP (cAMP) is one of the most widely used second messengers
Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

22. Conversion of ATP to cAMP to AMP
Fig
Conversion of ATP to cAMP to AMP
Adenylyl cyclase
Phosphodiesterase
Pyrophosphate P P i
ATP
cAMP
AMP
Figure Cyclic AMP

23. Triggering the making of cAMP
Many signal molecules trigger formation of cAMP
cAMP 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.
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

24. First messenger Adenylyl cyclase G protein GTP G protein-coupled
Fig
First messenger
Adenylyl
cyclase
G protein
G protein-coupled
receptor
GTP
ATP
Second
messenger
cAMP
Figure cAMP as second messenger in a G-protein-signaling pathway
Protein
kinase A
Cellular responses

25. Calcium Ions
Calcium ions (Ca2+) act as a second messenger in many pathways
Calcium is an important second messenger because cells can regulate its concentration
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

26. EXTRACELLULAR FLUID Plasma membrane Ca2+ pump ATP Mitochondrion
Fig
EXTRACELLULAR
FLUID
Plasma
membrane
Ca2+ pump
ATP
Mitochondrion
Nucleus
CYTOSOL
Ca2+
pump
Endoplasmic
reticulum (ER)
Figure The maintenance of calcium ion concentrations in an animal cell
Ca2+
pump
ATP
Key
High [Ca2+]
Low [Ca2+]

27. Step 3: Response
In Step 3, Response: Cell signaling leads to regulation of transcription or a change in the cell’s activities. This is sometimes called the “output response”.
Transcription: One of the processes involved in genes that determines which proteins will be made in the cell
Other cell signaling pathways may regulate the action of an enzyme.

28. Growth factor Reception Receptor Phosphorylation cascade Transduction
Fig
Growth factor
Reception
Receptor
Phosphorylation
cascade
Transduction
CYTOPLASM
Inactive
transcription
factor
Active
transcription
factor
Figure Nuclear responses to a signal: the activation of a specific gene by a growth factor
Response P
DNA
Gene
NUCLEUS
mRNA

29. The stimulation of glycogen breakdown by epinephrine:
Fig
Reception
Binding of epinephrine to G protein-coupled receptor (1 molecule)
Transduction
Inactive G protein
The stimulation of glycogen breakdown by epinephrine:
Active G protein (102 molecules)
This is an example of a phosphory-
lation
cascade
Inactive adenylyl cyclase
Active adenylyl cyclase (102)
ATP
Cyclic AMP (104)
Inactive protein kinase A
Active protein kinase A (104)
Figure Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine
Inactive phosphorylase kinase
Active phosphorylase kinase (105)
Inactive glycogen phosphorylase
Active glycogen phosphorylase (106)
Response
Glycogen
Glucose-1-phosphate
(108 molecules)

30. Changes in signal transduction pathways
Changes in signal transduction pathways can alter cellular response.
For Example: Conditions where signal transduction is blocked or defective can be deleterious (bad), preventative, or prophylactic (good).

31. What would happen if one of the relay molecules was defective?
Fig. 11-UN1
What would happen if one of the relay molecules was defective? 1
Reception 2
Transduction 3
Response
Receptor
Activation
of cellular
response
Relay molecules
Signaling
molecule

32. Question: how does caffeine work on the brain?
Caffeine has many effects on the body, but the most noticeable is that it keeps us awake.
The caffeine molecule is large and polar, so it doesn’t diffuse easily across the cell membrane.
Instead it binds to receptors on the surfaces of nerve cells in the brain.

33. adenosine
Adenosine (a nucleoside) accumulates in the brain when a person is under stress or has prolonged mental activity.
When it binds to a specific receptor in the brain, adenosine sets in motion a signal transduction pathway that results in reduced brain activity, which usually means drowsiness.

34. Caffeine and adenosine
Caffeine has a 3-dimensional structure similar to adenosine and is able to bind to the adenosine receptor.
Because its binding does not activate the receptor, caffeine functions as a antagonist of adenosine signaling, with the result that the brain stays active.
Caffeine
Adenosine

35. caffeine
Because caffeine has bound to the adenosine receptor, the adenosine has little effect, and the person stays awake.
The binding of caffeine to the adenosine receptor, however, is a reversible reaction. In time, the caffeine molecules come off the adenosine receptors in the brain, allowing adenosine to bind once again.

36. Additional effects of caffeine
In addition to competing with adenosine for a membrane receptor, caffeine blocks the enzyme cAMP phosphodiesterase.
This enzyme breaks down cAMP, which is a second messenger in the pathway that turns glycogen into sugar which is then released into the bloodstream.
Can you see how caffeine increases the “fight or flight” response?