Secondary massenger

1. Secondary Messengers
Wtf????

2. Secondary Messengers
Second messengers are molecules that relay signals received at
receptors on the cell surface — such as the arrival of protein
hormones, growth factors, etc. — to target molecules in the
cytosol and/or nucleus. But in addition to their job as relay
molecules, second messengers serve to greatly amplify the
strength of the signal.
In other terms, secondary messengers are those that help
communicate signals from cell surface to specific target sites
within cells (cytoplasm/nucleus).
Their main function is to transmit the signals as well as amply
it

4. There are 3 major classes of second messengers:
1.cyclic nucleotides (e.g., cAMP and cGMP)
2.inositol trisphosphate (IP3) and diacylglycerol (DAG)
3.calcium ions (Ca2+)

5. Cyclic nucleotide
A cyclic nucleotide (cNMP) is a single-phosphate
nucleotide with a cyclic bond arrangement between
the sugar and phosphate groups

6. Cylic AMP (cAMP)
• Cylic AMP (cAMP) is a water-soluble second messenger found
in eukaryotic and prokaryotic cells. The intracellular
concentrations of cyclic AMP are approximately 0.1-1.0 μM,
increasing 20-fold within seconds of activation. Cyclic AMP is
rapidly and continuously catabolized to adenosine 5′
monophosphate (5′-AMP) by cytosolic and particulate
formsphosphodiesterases (PDEs)(Fig. 2). PDE activity is
regulated through phosphorylation by protein kinase A
(PKA)and protein kinase C (PKC)Krebs (1989), Nishizuka
(1989).

7. cAMP system
• First messenger: Epinephrine (α2, β1, β2)
Acetylcholine (M2)
• First messenger Hormone :
ACTH, ANP, CRH, CT, FSH, Glucagon, hCG, LH, MSH, PTH, TSH
• Signal Transducer: GPCR/Gs (β1, β2), Gi (α2, M2)
• Primary effector: Adenylyl cyclase
• Secondary Messenger: cAMP (cyclic adenosine monophosphate)
• Secondary effector: protein kinase A

10. • The ligand binds to the GPCR altering the structure of that receptor
• Due to the binding of the ligand the receptor acts as GEF (guanine
nucleotide exchange factor) which causes detachment of G alpha subunit
because of conversion of GDP to GTP
• As the G alpha subunit is detached it moves across the membrane and
binds to the primary effector called Adenylyl Cyclase which converts ATP
to cAMP
• The cAMP then activates Protein Kinase A which further phosphorylate
other proteins leading to the cell response

11. Conversion of Inactive PKa to active PKa