Of note, the existence of a cAMP-dependent protein kinase A (PKA) phosphorylation site (S685) in GRK2 close to the calpain cleavage site raises the possibility of a regulatory interplay between protein phosphorylation and calpain-mediated degradation of GRK2 in the context of myocardial and cerebral ischemia, which are conditions characterized by a potent activation of PKA. This evidence concerns the gene GRK2 and brain ischemia.