BIO200H5 Lecture Notes - Lecture 6: Protein Kinase, Phosphodiesterase, Agonist
Slide 10
• Will mostly use cAMP as a second messenger
• The function of cAMP is to activate protein kinase by binding to its regulatory subunit
• Going to be converted AMP by the enzyme phosphodiesterase, because if it is constantly being
used then the cell will continuously be using energy
• These are inhibitors of PDE, by inhibiting PDE you keep cAMP more available in the cell even in the
absence of the ligand, even if G-proteins are deactivated
• This is not the only way to inhibit this secondary effect
Slide 11
• GPCRs are going to be deactivated by this mechanism
• The line represents the response
• Whenever there is binding to the agonist to the receptor, immediately the receptor will be
activated
o Ligand binding to the receptor, conformational changes will induce activation of G-protein
• There is then desensitization, this happens even in the presence of the ligand
o This will help these GPCRs to be activated by the arrival of a new ligand
• There is then inactivation, this is when there is no ligand
• GPCRs will return to its resting status
• There will be another deactivation and then re-activation
• Agonist will bind to receptor and receptor is activated (1-2)
o 1-2 = activation of receptor
• When there is activation of G-protein, GDP is going to bind and then the dissociation of alpha,
beta, and gamma subunits
• When there is no need for more G-protein to be activated, because we do have cAMP and cAMP
will do the work until it will be deactivated by PDE
• In this case, we want to spare the function of the receptor
• This space will occur by the presence of certain kinase (GPCR kinase)
o This will use ATP to phosphorylate the receptor (the 3 OH on the C-terminus of the receptor)
o The P groups are going to be phosphorylated
o This receptor is going to be tagged by the GPCR kinase enzyme
