Transcript Second Messengers & Protein Kinases

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 PKA
3. 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 cell
in 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
Liver
glucagon
Bone resorption
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 b-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