Chapter 23: Signal Transduction

Epinephrine —> Glycogen Phosphorylase Activation

1. Epinephrine binds B-adrenergic receptor (GPCR)

2. Conformational change in receptor

3. G protein exchanges GDP —> GTP

4. Ga - GTP activates adenylyl cyclase

5. Adenylyl cyclase produces cAMP

6. cAMP activates PKA

7. PKA phosphorylates phosphrylase kinase

8. Phosephorylase kinase phosphorylates glycogen phosphorylase b → a

G protein cycle: inactive

GDP - bound, aBy complex together

G protein cycle: activation

GTP releases GDP, dissociates By

G protein cycle: termination

GTPase activity hydrolyzes GTP → GDP

ER Calcium Release: Trigger

PLC cleaves PIP2 → IP3 + DAG

ER Calcium Release: IP3

Binds receptors on ER, releases Ca2+

ER Calcium Release: DAG

activiates PKC with Ca2+

ER Calcium Release: PKC role

phosphorylates proteins for cellular response

Insulin → ERK phosphorylation:

1. Insulin binds receptor tyrosine kinase

2. Receptor autophosphorylation

3. IRS proteins recerutied and phosphorylated

4. Grb 2 - SOS complex binds

5. SOS activates Ras (GDP → GTP)

6. Ras - GTP activates Raf

7. Raf phosphorylates MEK

8. MEK phosphorylates ERK

GCPR Densitization by Insulin

1. Insulin activates PKB / AKT via PI3K pathway

2. PKB phosphorylates B - arrestin

3. B - arrestin binds phosphorylated GPCRs

4. Prevents G protein coupling (densensitization)