PKCs are involved in many cellular processes, and thus the downstream substrates of PKCs are numerous. They include several neurotransmitter receptors such as the α4nAChreceptor which can be PKC phosphorylated on Ser-550;158 dopamine D2 receptors phosphorylated by PKC at Ser-229, Ser-228, Thr-352, Thr-354, and Ser-355;159 and CB1 receptors phosphorylated by PKC at Ser-317.160 Other PKC substrates include proteins involved in exocytosis (including Ser-187 of SNAP-25)161 as well as proteins important in synaptic plasticity (such as Ser-36 of neurogranin162 and Ser-41 of neuromodulin).163 In addition, PKC phosphorylates Ser-818 of GluR1, facilitating AMPA receptor externalization and LTP.164 Thus, PKCs may play an important role in drug-induced synaptic plasticity.
