1. Seven-Transmembrane Receptor Signaling Heterotrimeric G-proteins & Second Messenger Pathways

2. 7TM Receptor Interacting with Trimeric G- Protein

3. Canonical 7TM Signaling Pathway - I Activated receptor Binds heterotrimeric G-protein (G  ) –specific ones for specific receptors Activated receptor is GEF –exchanges GDP for GTP on G  –G  dissociates from G  G  activates/inhibits downstream transducers –adenylyl cyclases –phosphodiesterases –phospholipases G  activates/inhibits downstream transducers –inhibition of kinases that inactivate 7TM receptors

4. Canonical 7TM Signaling Pathway – II Adenylyl cyclase –synthesis if cAMP ([cAMP] increase 100X) –cAMP activates protein kinase A (PKA) PKA (S/T kinase) –regulated by RII (regulatory II) subunit RII subunit is binds cAMP or PKA catalytic subunit –deregulation by cAMP allows PKA to phosphorylate numerous substrates –PKA can enter nucleus and phosphorylate many transcriptions factors activates and inhibits

5. Canonical 7TM Signaling Pathway – III Turning off the signals –RGS – regulators of G-protein signaling) GAPs for G  subunits that stimulate GTP hydrolysis hydrolysis allows G  reassociation –downstream kinases phosphorylate 7TM receptors blocks further G protein stimulation

6. Cyclic Nucleotides

7. Adenylyl Cyclase Converts ATP to cAMP Stimulated by G s  Inhibited by G i 

8. Removal of Cyclic Nucleotides Phosphodiesterases cut 3'-O-P bond to generate 5' nucleoside monophosphates cAMP AMP cGMP GMP Phosphodiesterase

9. Cyclic Nucleotide Activated Kinases Protein kinases –PKA cAMP cAMP binds to RII subunit releases PKA from autoinhibition –PKG cGMP

10.  -Andrenergic Receptors

11. Formation of Lipid 2 nd Messengers

12. Lipid Second Messengers & Targets

13. Lipid 2 nd Messenger Activated Protein Kinases Protein Kinase C Family

14. Phosphoinositol Second Messenger Signaling

15. Ca 2+ Second Messenger Signaling

16. Odorant Receptors

17. Photoreceptors

18. Eicosanoids