1. Cell Signaling
How to Get a Message from the outside of the Cell to the inside of the cell

2. 1. Reception
2. Transduction
3. Response

3. G-Protein Linked Receptors
Transmembrane Protein (“trans” means “across”, so this protein goes “across” the membrane)
7 Alpha helices
Outside: Signal molecule binding site.
When a signal molecule (also called a ligand) binds to the signal binding site, this causes the G-Protein Linked Receptor to change shape
e.g. this signal molecule can be epinephrine (adrenaline)
Inside: Changes in G-Protein linked receptor causes another molecule called a G-Protein to change from an inactive to an active state.

4. G-Protein Linked Receptors and G-Proteins
G-Protein Linked Receptor is different from a G-Protein (see illustration)
G-Protein Linked Receptor
A transmembrane protein- introduced in the last slide
Detects the signal and changes shape (hence the name “receptor”)
Has “G-Protein” as part of the name because it will also bind with a “G-Protein” inside the cell
G-Protein
Named “G-protein” because GDP is bound to it (GDP is similar to ADP)
Located on the inner membrane of the cell
When GDP is bound to it, it is in its inactive state

5. G-Protein Linked Receptors and G-Proteins
Process:
Signal molecule binds to G- Protein Linked Receptor
G-Protein Linked Receptor changes shape
G-Protein Linked Receptor binds to G-Protein (which is inactive)
G-Protein Activation causes GDP to be replaced by GTP
G-Protein with GTP is now in its active form

6. G-Protein Linked Receptors and G-Proteins
G-Protein dissociates from the G-Protein Linked Receptor
G-Protein diffuses along the membrane
Binds to an enzyme
This binding activates the enzyme
Results in a cellular response.

7. CELLULAR RESPONSE AND THE Second Messenger
Adenylyl Cyclase is a common enzyme in these signally pathways
It catalyzes the conversion of ATP to cyclic AMP
Cyclic AMP (cAMP) is known as a second messenger

8. Second Messenger Adenylyl Cyclase
Enzyme that catalyzes ATP->cyclic AMP
Cyclic AMP (cAMP) is the second messenger
See structure below

9. Second Messenger
cAMP activates another protein
Protein Kinase A

10. Phosphorylation Cascade
Protein Kinase
Enzyme that catalyzes the transfer of phosphate groups from ATP to a protein
2% of our genome codes for these enzymes!!

11. Phosphorylation Cascade
Protein Phosphatases
Enzyme that catalyzes the removal of phosphate groups from proteins
Reverse of what protein kinases do.

12. Epinephrine

13. G-Protein Linked Receptors and G-Proteins
G-Protein Inactivation
G-Protein acts as GTPase
Breaks down GTP to GDP
Unbinds from enzyme
Becomes inactive again

14. Three Step Process
1. Reception
2. Transduction
3. Response

15. Animations
G-Protein Cell Signaling

16. Is Cell Signaling Important?
Earl Sutherland discovered how epinephrine (adrenaline) works to increase glucose to the cells to aid in the “fight or flight response.”
-Free Response #1 tonight

17. G-Protein Linked Receptors
Are G-Protein Linked Receptors really that important?

18. Tyrosine-Kinase Receptors

19. Tyrosine-Kinase Receptors

20. Tyrosine-Kinase Receptors

21. Tyrosine-Kinase Receptors

22. Ion Channel Receptors

23. Ion Channel Receptors

24. Ion Channel Receptors

25. Second Messengers
Cyclic AMP
Calcium ions

26. Calcium Ions

27. Calcium Ions and IP3

28. Growth Factors and Stimulation of Transcription

29. Signal Molecules G-Protein Linked Receptors
Hormones, neurotransmitters, odors, light sensitive compounds
Involved in bacteria infections
60% of all medicines today exert their effects by influencing G-protein pathways.
Two Principle Signal Transduction Pathways
Cyclic AMP signal pathway
Phosphatidylinositol (PIP) signal pathway
Tyrosine Kinase Receptors
Growth factors (cell growth, cell reproduction) hormones (insulin), cytokines, can cause cancer