Second Messengers & Protein Kinases

Lecture 27 BSCI 420/421 Nov 2002

“When you reach the end of your rope, tie a knot and hang on” -Anon

1. Protein kinases 2. cAMP and PKA3. IP3. DAG, Ca2+, PKC & CaM Kinase,Lecture 27

Protein kinase structure and Evolutionary Tree

(PKA)

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

2. cAMP and PKA

a. cAMP synthesis cAMP increase in a nerve cellin response to serotonin

Activation of PKA by cAMP

Gene & Enzyme

Activation by PKA

Inactive ->Active enzyme

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.

Table 15-1 cAMP mediated responses

Thyroid gland TSH Thyroid hormone secretion

Adrenal cortex ACTH Cortisol secretion

Ovary LH Progesterone secretion

Muscle Adrenaline glycogen breakdown

Bone parathormone Bone resorption

Liver glucagon glycogen 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)

2. IP3. DAG, Ca2+, PKC & CaM Kinase

The inositol phospholipid pathway

Ca2+ control

Calmodulin

Regulation of CaM-Kinase II