Alicia Hobdell
MSP’23
Task 10: The Dual Role of Insulin
Insulin Receptor 3. Akt is phosphorylated by mTOR kinase on
a serine then by PDK1on a threonine,
Receptor tyrosine kinase (= enzyme-coupled
causing its activation.
receptor); insulin receptor is a dimer that
4. Activated Akt dissociates from the plasma
comprises two α-chains and two β-chains.
membrane and phosphorylates target
● Binding of insulin to the RTK stimulates
proteins (e.g., Bad)
carbohydrate utilization and protein
Survival
synthesis
● Binding of insulin-like growth factor (IGF1)
to the RTK stimulates cell growth and
survival in many cell types
Binding of a ligand to
the α-subunit of the
RTK →
conformational Bad holds apoptosis-inhibitory proteins (Bcl2 in an
change → brings the inactive state
β-chains closer 1. Bad phosphorylation releases the
together → inhibitory proteins, blocking apoptosis and
phosphorylate each promoting cell survival.
other on tyrosines. Glucose Uptake
Insulin Signaling Pathways
The tyrosine-kinase receptor system allows the cell
to trigger several signal transduction pathways and
cellular responses at once.
PI-3-Kinase–Akt Signaling Pathway
1. AKT catalyzes the phosphorylation of
AS160, stimulating the translocation of
1. Binding of IGFs or insulin to specific RTKs GLUT4 (= glucose transporter) from the
recruits and activates PI-3-kinase GLUT4 storage vesicles (GSV) in the
2. The PI-3-kinase phosphorylates PI(4,5)P2 cytoplasm to the cell membrane.
to PI(3,4,5)P3, which serves as a docking 2. GLUT4 accumulation in the plasma
site for Akt (= protein kinase B, PKB) and membrane promotes glucose uptake by
phosphoinositide-dependent protein the liver and adipose tissue → decrease in
kinase 1 (PDK1) via their PH domains, blood glucose concentration
bringing them into proximity at the plasma
membrane
MSP’23
Task 10: The Dual Role of Insulin
Insulin Receptor 3. Akt is phosphorylated by mTOR kinase on
a serine then by PDK1on a threonine,
Receptor tyrosine kinase (= enzyme-coupled
causing its activation.
receptor); insulin receptor is a dimer that
4. Activated Akt dissociates from the plasma
comprises two α-chains and two β-chains.
membrane and phosphorylates target
● Binding of insulin to the RTK stimulates
proteins (e.g., Bad)
carbohydrate utilization and protein
Survival
synthesis
● Binding of insulin-like growth factor (IGF1)
to the RTK stimulates cell growth and
survival in many cell types
Binding of a ligand to
the α-subunit of the
RTK →
conformational Bad holds apoptosis-inhibitory proteins (Bcl2 in an
change → brings the inactive state
β-chains closer 1. Bad phosphorylation releases the
together → inhibitory proteins, blocking apoptosis and
phosphorylate each promoting cell survival.
other on tyrosines. Glucose Uptake
Insulin Signaling Pathways
The tyrosine-kinase receptor system allows the cell
to trigger several signal transduction pathways and
cellular responses at once.
PI-3-Kinase–Akt Signaling Pathway
1. AKT catalyzes the phosphorylation of
AS160, stimulating the translocation of
1. Binding of IGFs or insulin to specific RTKs GLUT4 (= glucose transporter) from the
recruits and activates PI-3-kinase GLUT4 storage vesicles (GSV) in the
2. The PI-3-kinase phosphorylates PI(4,5)P2 cytoplasm to the cell membrane.
to PI(3,4,5)P3, which serves as a docking 2. GLUT4 accumulation in the plasma
site for Akt (= protein kinase B, PKB) and membrane promotes glucose uptake by
phosphoinositide-dependent protein the liver and adipose tissue → decrease in
kinase 1 (PDK1) via their PH domains, blood glucose concentration
bringing them into proximity at the plasma
membrane
