Hormones & Signal Transduction 5 Sections28 LessonsLifetime
cAMP & PIP2 System
The cAMP and the PIP2 pathways are compared together for better understanding of the sequences involving the 5 main steps regarding the signal transduction through cell surface receptors in water soluble hormones.
The cAMP Pathway
The hormones that work through the cAMP pathway are:
- Epinephrine β (Gs)
- Epinephrine α2 (Gi)
- Acetylcholine M2 (Gi)
- Dopamine & Serotonin both (Gs & Gi)
- TSH (Gs)
- Vasopressin in kidneys (Gs)
Remember the 5 steps told in the previous lesson.
In the first step the hormone binds to the receptor. This receptor is a single protein having 7 transmembrane domains.
The receptor that has 7 transmembrane domains is a G Protein receptor.
This binding of the hormone activates the G Protein inside the membrane (hormone binding is outside the membrane).
Now if the signal is stimulatory (Gs) then it will activate the enzyme Adenyl cyclase, but if it Gi then it will inhibit the enzyme.
Adenyl cyclase will then increase the production of cAMP through the production of ATP.
cAMP then in turn will activate the Protein kinase A.
Protein kinase A will in turn will work on two different pathways:
On one side it will activate the Protein kinases in the cell. These Protein kinases will phosphorylate the enzymes.
One the other side Protein kinase A will phosphorylate CREB.
The phosphorylated CREB will enter the nucleus and will activate the CRE.
CRE in turn will activate gene and thus inducing transcription.
The PIP2 Pathway System
The hormones that work through the PIP2 system are:
- Vasopressin
- Epinephrine α1 (Gi)
- Acetylcholine M1, M3
Steps
This pathway has the similar steps except the G Protein involved is “Gq” protein.
When the hormone binding activates the Gq protein, it in turn activates the enzyme Phospholipase C.
Phospholipase C acts on PIP2 in the membrane and divides it into to components –
IP3 & DAG (2 second messengers).
IP3 enters the cytoplasm and binds to the receptors on the ER.
This opens the Calcium channels and activates the release of Ca+2 into the cytoplasm.
Now from here the Ca+2 also acting as a second messenger, in combination with DAG that remained in the membrane, will activate Protein Kinase C.
Once activated the Protein kinase C will induce Gene Expression by a pathway other than CREB (DOES NOT involve CREB).
On the other side it will also activate Protein Kinases in the cell that will phosphorylate enzymes.