1. Second Messengers & Protein Kinases Lecture 27BSCI 420/421Nov 2002 “When you reach the end of your rope, tie a knot and hang on” -Anon 1.Protein kinases 2.cAMP and PKA 3.IP3. DAG, Ca2+, PKC & CaM Kinase,Lecture 27

2. Protein kinase structure and Evolutionary Tree (PKA)

3. 1.Protein kinases, e.g. PKA - A ser, thr kinase

4. 2. cAMP and PKA a.cAMP synthesiscAMP increase in a nerve cell in response to serotonin

5. Activation of PKA by cAMP

6. Gene & Enzyme Activation by PKA Inactive ->Active enzyme

7. Reversal of stimulus ~1 min When signal molecule releases, Receptor returns to initial state, Galpha hydrolyses GTP -> GDP & releases from enzyme, Adenylate cyclase becomes inactive, G subunits form trimer again, cAMP ->AMP by phosphodiesrease, PKA C subunits bind to R subunits and becomeinactive, P-Proteins -> Protein + Pi by protein phosphatase Some receptors release inhibitory Galphai, Which binds to AC and inhibits its activity. Eg. Prostaglandin E1 binds to inhib receptor and counteracts Epinephrine activity.

8. Table 15-1 cAMP mediated responses Thyroid gland TSHThyroid hormone secretion Adrenal cortex ACTHCortisol secretion Ovary LHProgesterone secretion MuscleAdrenalineglycogen breakdown BoneparathormoneBone resorption Liverglucagonglycogen breakdown The same hormone can have the diff effects in diff cells. Adrenalin (epinephrine) above, or stim heartbeat rate in heart muscle cells. How? Same  adrenergic receptors. Diff. Enzymes activated in diff cell types. (Beta blockers-propanolol)

9. 2. IP3. DAG, Ca2+, PKC & CaM Kinase The inositol phospholipid pathway

11. Ca2+ control

12. Calmodulin

13. Regulation of CaM-Kinase II