Intracellular signalling

Intracellular signalling

1. Cholera

   • Vibrio cholerae produces cholera toxin
     • Cholera toxin modifies α subunit of Gs
   • 1. Toxin inhibits GTPase
     • 2. Hydrolysis of GTP prevented
       • 3. Prolonged activation of Gs and adenylyl cyclase
         • 4. Increased levels of cAMP
           • 5. Excess flow of water in GI tract leads to diarrhoea

2. Whooping cough

   • Bordetella pertussis produces pertussis toxin
     • Pertussis toxin modifies α subunit of Gi
   • 1. Pertussis toxin prevents GPCR interaction with Gi
     • 2. Blocks activation of α subunit
       • 3. Prevents Gi inhibiting adenylyl cyclase
         • 4. Increased levels of cAMP

3. Adenylyl cyclase

   • Adds phosphate to ATP in cyclic arrangement
   • 1. Effector enzyme activated by Gαs
     • 2. Adenylyl cyclase converts ATP to cAMP
       • 3. cAMP phosphodiesterase converts cAMP to a linear phosphate

4. Inositol phospholipid pathway

   • Phospholipase C acts as an effector
   • 1. Hormone binds to receptor
     • 2. Activated G protein activate phospholipase C
       • 3. Acts on inositol phospholipid PIP2
         • 4. Phospholipid is hydrolysed into DAG and InsP3
           • 5. InsP3 opens calcium ion channels

5. Cyclic AMP pathway

   • Activation of adenylyl cyclase leads to increased cAMP
     • cAMP phosphodiesterase converts cAMP to linear phosphate
   • cAMP activates cAMP-dependent PKA
     • PKA phosphorylates proteins
   • Glycogen metabolism
     • Increased cAMP activates glycogenolysis
     • Decreased cAMP activates glycogenesis