1. Figure 11.11 Adenylyl cyclase Phosphodiesterase Pyrophosphate AMP
P i
ATP
cAMP
AMP
Figure Cyclic AMP.

2. Many signal molecules trigger formation of cAMP
Other components of cAMP pathways are G proteins, G protein-coupled receptors, and protein kinases
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

3. First messenger (signaling molecule such as epinephrine)
Figure 11.12
First messenger (signaling molecule such as epinephrine)
Adenylyl cyclase
G protein
G protein-coupled receptor
GTP
ATP
Second messenger
cAMP
Figure cAMP as a second messenger in a G protein signaling pathway.
Protein kinase A
Cellular responses

4. Calcium Ions and Inositol Triphosphate (IP3)
Calcium ions (Ca2+) act as a second messenger in many pathways
Calcium is an important second messenger because cells can regulate its concentration

5. Endoplasmic reticulum (ER)
Figure 11.13
EXTRACELLULAR FLUID
Plasma membrane
Ca2 pump
ATP
Mitochondrion
Nucleus
CYTOSOL
Ca2 pump
Figure The maintenance of calcium ion concentrations in an animal cell.
Endoplasmic reticulum (ER)
Ca2 pump
ATP
Key
High [Ca2 ]
Low [Ca2 ]

6. A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol
Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers

7. Signaling molecule (first messenger)
Figure
EXTRA- CELLULAR FLUID
Signaling molecule (first messenger)
G protein
DAG
GTP
G protein-coupled receptor
PIP2
Phospholipase C
IP3 (second messenger)
IP3-gated calcium channel
Figure Calcium and IP3 in signaling pathways.
Various proteins activated
Cellular responses
Endoplasmic reticulum (ER)
Ca2
Ca2 (second messenger)
CYTOSOL

8. Concept 11.4: Response: Cell signaling leads to regulation of transcription or cytoplasmic activities
The cell’s response to an extracellular signal is sometimes called the “output response”

9. Nuclear and Cytoplasmic Responses
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

10. Inactive transcription factor Active transcription factor
Figure 11.15
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

11. Other pathways regulate the activity of enzymes rather than their synthesis

12. Glucose 1-phosphate (108 molecules)
Figure 11.16
Reception
Binding of epinephrine to G protein-coupled receptor (1 molecule)
Transduction
Inactive G protein
Active G protein (102 molecules)
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)

13. Signaling pathways can also affect the overall behavior of a cell, for example, changes in cell shape

14. Wild type (with shmoos) Fus3 formin CONCLUSION
Figure 11.17
RESULTS
Wild type (with shmoos)
Fus3
formin
CONCLUSION 1
Mating factor activates receptor.
Mating factor
Shmoo projection forming
G protein-coupled receptor
Formin P
Fus3
Actin subunit
GTP P
GDP 2
Phosphory- lation cascade
G protein binds GTP and becomes activated.
Formin
Formin
Figure Inquiry: How do signals induce directional cell growth during mating in yeast? P 4
Fus3 phos- phorylates formin, activating it.
Microfilament
Fus3
Fus3 P 5
Formin initiates growth of microfilaments that form the shmoo projections. 3
Phosphorylation cascade activates Fus3, which moves
to plasma membrane.

15. Fine-Tuning of the Response
There are four aspects of fine-tuning to consider
Amplifying the signal (and thus the response)
Specificity of the response
Overall efficiency of response, enhanced by scaffolding proteins
Termination of the signal

16. Signal Amplification Enzyme cascades amplify the cell’s response
At each step, the number of activated products is much greater than in the preceding step

17. The Specificity of Cell Signaling and Coordination of the Response
Different kinds of cells have different collections of proteins
These different proteins allow cells to detect and respond to different signals
Even the 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

18. Figure 11.18
Signaling molecule
Receptor
Relay molecules
Activation or inhibition
Figure The specificity of cell signaling.
Response 1
Response 2
Response 3
Response 4
Response 5
Cell A. Pathway leads to a single response.
Cell B. Pathway branches, leading to two responses.
Cell C. Cross-talk occurs between two pathways.
Cell D. Different receptor leads to a different response.

19. 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
In some cases, scaffolding proteins may also help activate some of the relay proteins

20. Three different protein kinases
Figure 11.19
Signaling molecule
Plasma membrane
Receptor
Three different protein kinases
Figure A scaffolding protein.
Scaffolding protein

21. Termination of the Signal
Inactivation mechanisms are an essential aspect of cell signaling
If ligand concentration falls, fewer receptors will be bound
Unbound receptors revert to an inactive state

22. Concept 11.5: Apoptosis integrates multiple cell-signaling pathways
Apoptosis is programmed or controlled cell suicide
Components of the cell are chopped up and packaged into vesicles that are digested by scavenger cells
Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells

23. Figure 11.20
Figure Apoptosis of a human white blood cell.
2 m

24. Apoptosis in the Soil Worm Caenorhabditis elegans
Apoptosis is important in shaping an organism during embryonic development
The role of apoptosis in embryonic development was studied in Caenorhabditis elegans
In C. elegans, apoptosis results when proteins that “accelerate” apoptosis override those that “put the brakes” on apoptosis

25. Ced-9 protein (active) inhibits Ced-4 activity
Figure 11.21
Ced-9 protein (active) inhibits Ced-4 activity
Ced-9 (inactive)
Cell forms blebs
Death- signaling molecule
Mitochondrion
Active Ced-4
Active Ced-3
Other proteases
Ced-4
Ced-3
Nucleases
Receptor for death- signaling molecule
Activation cascade
Figure Molecular basis of apoptosis in C. elegans.
Inactive proteins
(a) No death signal
(b) Death signal

26. 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

27. 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, Parkinson’s and Alzheimer’s); interference with apoptosis may contribute to some cancers

28. Cells undergoing apoptosis
Figure 11.22
Cells undergoing apoptosis
Space between digits
1 mm
Interdigital tissue
Figure Effect of apoptosis during paw development in the mouse.