Epinephrine and Insulin Biosignaling Pathways

Epinephrine binding pathway

1. epinephrine binds to beta adrenergic receptor

2. activated receptor + G protein alpha, beta, gamma

3. GTP replaces GDP

4. activated G protein alpha subunit

   • GTP hydrolyzed to GDP by intrinsic GTPase → G protein aBy

5. protein-protein interaction

6. activated adenylate cyclase

7. enzymatic rxn

8. increased cAMP

   • cAMP phosphodiesterase → non-active 5’-AMP

9. activated protein kinase A (PKA) and other effectors

10. kinase phosphorylated

11. glycogen phosphorylase

12. glucose release

Insulin signaling cascade pathway

1. insulin binds to receptor (alpha subunits, extracellular)

2. insulin receptor activated (beta subunits, intracellular) + insulin receptor substrate -1 (IRS-1)

3. IRS-1 becomes phosphorylated and binds to phospinositide-3 kinase (PI3K)

4. activated PI3K + PIP2 phosphorylation

5. PIP3 + PIP3 dependent kinase (PDK1)

6. activated PDK1 + protein kinase B (Akt) phosphorylation

7. phosphorylated Akt

8. further signaling leads to movement of glucose transporter GLUT-4 from storage to plasma membrane

9. glucose uptake

Insulin receptor activates a multivalent signaling protein cascade pathway

1. insulin binds to receptor (alpha subunits, extracellular)

2. insulin receptor activated (beta subunits, intracellular) + insulin receptor substrate -1 (IRS-1)

3. IRS-1 becomes phosphorylated and binds to SH2 domain of Grb2

4. binding to Sos

5. binding to RAS

6. binding to activated RAS + Raf-1, GTP replaces GDP

7. binding to activated Raf-1 phosphorylates MEK

8. MEK phosphorylates ERK on Thr and Tyr residue

9. ERK enters nucleus → phosphorylates Elk1 (transcription factor)

10. phosphorylates Elk1 joins SRF to stimulate expression of specific genes needed for cell division

What is the major difference between insulin binding to phosphinostide-3 kinase (PI3K) and to Grb2?

PI3K → glucose uptake

Grb2 → stimulates expression of specific genes