Protein Kinase A

links: reference: 10-4-2021

Protein Kinase A (PKA) (cAMP-dependent protein kinase) #

Family of Enzyme dependent on cAMP for its Phosphate.

• Heterotetrmeric: two regulatory (R I/II, α/β subunits for each) and two catalytic (C) subunits.
• Each R binds to 2x cAMP. Afterwards, the Cs dissociate.
  • Notice, they have no cAMP and are just now-active kinases: they catalyze dephosphorylation of ATP to hydroxyls on serine-threonine residues on substrate proteins.
    • These proteins in include both voltage- and ligand-gated Ion Channels, synaptic vesicle proteins, transmitter synthesis enzymes, and things like CREB, affecting transcription.
    • How do they make it back to the R subunits after PDE, and how tf do the C subunits get deactivated? Maybe afterwards they just swim around and the cytoplasm is ‘saturated’ with them and it just gets new ones waits for them to come back around.
• The R subunits (thus basically the thing as a whole) orient/move/’target’ for the C subunits to distinct sites:
  • Type II PKA (has $R_I$ and $R_{II}$) targets A kinase attachment proteins (AKAPs), of which there are 13.
    • One binds PKA to PSD-95.
  • Type I PKA only weakly binds to AKAPs, so it is mostly free in the Cytoplasm.

Targets #

• Phosphorylates CREB directly, but inhibition of PP1 by phosphorylating DARPP-32 @ Thr34 is also necessary.
  • Eventually, CDK5, downstream of CREB, is able to inhibit PKA.
• PKA reudces PP1 activity directly, via phosphorylating the glycogen binding region, GM, which causes its dissociation from the catalytic PP1 unit. The separation of PP1, glycogen, etc. causes significant decrease in phosphorylation.