1. Chapter 15 Baboon text Cell Signaling and Communication 15
Chapter 15 Baboon text Cell Signaling and Communication What Are Signals, and How Do Cells Respond to Them?
Information that all cells receive can be a physical stimulus, such as light; or chemical and can come from outside the organism, or from neighboring cells.

2. Signal-Transduction Emphasis
This chapter’s emphasis is on signals that are released from one cell and allowed to freely diffuse to a second (or more) recipient cell(s)
These communications are deliberately initiated, received, and interpreted in order to increase the physiological coordination of the cells in multicellular organisms
We will consider in particular those events that follow the reception of chemical signals
We will not dwell on the purpose of the signal
We also will not dwell on why and how a given cell released a given signal

3. Chemical Signaling Between Cells
Three general categories of chemical signaling:
Necessary Vocabulary:
Ligand
Cytoplasmic connections between cells
Receptor
G-protein-linked receptor
Cell-to-cell contact-mediated signaling
Cytoplasmic G protein
Tyrosine kinases
Free diffusion between cells
Ligand-gated ion channels
Adjacent cells (within interstitial space)
Transduction/Transduced
Phosphorylization
Distant cells (hormones)
Cascades
Transcription factors

4. 15.1 What Are Signals, and How Do Cells Respond to Them?
Autocrine signals affect the cells that made them.
Paracrine signals affect nearby cells.
Hormones travel to distant cells, usually via the circulatory system.

5. Local Diffusion
e.g., Histamine released from damaged cells in inflammation
e.g., Interferon release by viral-infected cells

6. Three Stages of Signal Transduction
Reception of extracellular signal by cell
Transduction of signal from outside of cell to inside of cell—often multi-stepped
Note not necessarily transduction of ligand
Cellular Response
Response is inititiated and/or occurs entirely within receiving cell

7. Three Stages of Signal Transduction

8. Three Stages 1. Reception 2a. Transduction 2b. Transduction
2c. Transduction
2d. Transduction
3. Response
Responses usually involve increasing or decreasing some Protein’s Function

9. Three Stages 1. Reception 2a. Transduction 2b. Transduction
3. Response

10. Various Responses
Note that more than one response can result from the reception of a single ligand

11. A signal transduction pathway:
The signal causes receptor protein to change conformation.
Conformation change gives it protein kinase activity.
Phosphorylation alters function of a responder protein.

12. Various Responses

13. LIGANDS
Receptor proteins have very specific binding sites for chemical signal molecules, or ligands.
Binding the ligand causes receptor protein to change shape.
The binding is reversible.

14. Ligands Extracellular Reception Intracellular Reception
e.g., insulin and
epinephrine
e.g., nitric oxide and
steroid hormone

15. Examples of Surface Receptors

16. 15.2 How Do Signal Receptors Initiate a Cellular Response?
Types of plasma membrane receptors:
Ion channels
Protein kinases (Tyrosine-kinase receptors)
G protein-linked receptors

17. 15.2 How Do Signal Receptors Initiate a Cellular Response?
Ion channel receptors: channel proteins that allow ions to enter or leave a cell.
Example: acetylcholine that allows Na+ into cell

18. Figure 15.5 A Gated Ion Channel

19. Ion-Channel Receptors

20. 15.2 How Do Signal Receptors Initiate a Cellular Response?
G protein-linked receptors: the seven-transmembrane-spanning G protein-linked receptors.
G proteins: mobile membrane proteins with three subunits.

21. 15.2 How Do Signal Receptors Initiate a Cellular Response?
Signal outside cell activates G protein linked receptor which activates G protein inside cell.
This then activates the protein (by changing GDP to GTP) and it moves through plasma membrane until it encounters an effector protein.
Binding activates the effector which causes a change in cell function (activation/inhibition).

22. G Protein-Linked Receptors

23. Figure 15.7 A G Protein-Linked Receptor (Part 1)

24. Figure 15.7 A G Protein-Linked Receptor (Part 2)

25. G Protein-Linked Receptors
the more ligand binding, the more K+ in cytoplasm
G Protein-Linked Receptors
note how activation is reversible

26. 15.3 How Is a Response to a Signal Transduced through the Cell?
Protein kinase receptors—direct signal transduction.
When signal binds to protein kinase receptor, it changes conformation, exposing an active site to phosphorylate a target protein.

27. Protein Kinase & Phosphatase
Figure A Protein Kinase Cascade
Protein Kinase & Phosphatase

28. 15.4 How Do Cells Change in Response to Signals?
Opening ion channels is a key step in response of nervous system cells.
EXAMPLE: the sense of smell.
Odorant molecules bind to receptors in the nose, a G protein is activated.
This activates adenylyl cyclase to catalyze formation of cAMP, which opens ion channels. Influx of Na+ and Ca2+ stimulates nerves to send signals to the brain.

29. Figure 15.17 A Signal Transduction Pathway Leads to the Opening of Ion Channels (Part 1)

30. Figure 15.17 A Signal Transduction Pathway Leads to the Opening of Ion Channels (Part 2)

31. 15.4 How Do Cells Change in Response to Signals?
EXAMPLE
Changing enzyme activities:
Addition of a phosphate group by a protein kinase changes enzyme conformation.
cAMP binds to enzymes allosterically to change conformation.
In both, an active site is exposed, and enzyme catalyzes new reactions.

32. 15.4 How Do Cells Change in Response to Signals?
The signal is amplified in this pathway through many second messengers and phosphorylation:
Ex: For one molecule of epinephrine that arrives at plasma membrane,10,000 molecules of blood glucose result.

33. Figure 15.18 A Cascade of Reactions Leads to Altered Enzyme Activity (Part 1)

34. Figure 15.18 A Cascade of Reactions Leads to Altered Enzyme Activity (Part 2)

35. Tyrosine Kinase Receptors
Note steps involved:
Ligand Reception
Receptor Dimerization
Catalysis (Phosphorylization)
Subsequent Protein Activation
Further Transduction
Response

36. Tyrosine Kinase Receptors

37. Tyrosine Kinase Receptors

38. 15.3 How Is a Response to a Signal Transduced through the Cell?
In both, signal initiates a cascade of events.
A weak signal can be amplified, and distributed to cause several different responses in the target cell.

39. Signal Amplification (Cascade)

40. 15.3 How Is a Response to a Signal Transduced through the Cell?
Second messengers were discovered in research on the liver enzyme glycogen phosphorylase, and how it is activated by epinephrine. (Read up on Sutherland’s investigations with epinephrine p )
Binding of the hormone to the membrane receptor caused production of a small molecule (cyclic AMP, or cAMP) that diffused into the cytoplasm to activate the enzyme.

41. 15.3 How Is a Response to a Signal Transduced through the Cell?
The signal is the first messenger.
The second messenger is released into the cytoplasm after signal binds to receptor.
Second messengers affect many processes in the cell.
Also amplify the signal—one epinephrine molecule leads to production of many cAMP.
The last sentence needs to be complete…what also amplifies the signal?

42. Second Messengers

43. Cyclic AMP (cAMP) 2nd Messenger

44. Specificity of Cell Signaling
Note how same ligand gives rise to different responses
Cells differ in terms of their proteins
Different proteins respond differently to the same environental signals
(note, though, same receptors, different relay)
Different cells behave differently because some, but not all proteins can differ between cell types

45. Acknowledgements biology.ucf.edu/courses/bsc2010/08-2010C-02.PPT \
Acknowledgements

46. Putting the information to work

47. Cell Cycle Control System
How is the cell cycle controlled
Restriction Checkpoints- sites where cell division are either prevented or stopped
Locations
G1- commits the cell to division G2 M
Ex: At the G1 checkpoint, if the cycle is stopped, cell will enter G0

48. Checkpoints are controlled by protein activity
2 main proteins
Cyclins- proteins continually produced in cells
Kinases-proteins that activate or inactivate target proteins by phosphorylating them
Phosphorylation: breaking down ATP and adding a phosphate group
This changes the shape of the target protein
Target proteins –directly regulate the cell cycle

49. Ex: G1 checkpoint Proteins involved Cyclin
Cyclin dependent kinase (Cdk)
Rb (target protein) normally inhibits the cell cycle at G1 checkpoint
How it works
When Cdk binds with a cyclin, it becomes activated
Cdk/cyclin complex phosphorylates RB
Rb becomes inactive and can no longer inhibit the cell cycle
Cell proceeds to stage Synthesis
NOTE: RB and other target proteins in the cell cycle control system act as tumor suppressors by stopping uncontrolled cell division.

50. LOOK AT FIGURE 9.6 IN YOUR BABOON TEXT

51. Chemical Signaling Between Cells