PRECISION SUBSTRATE TARGETING OF PROTEIN-KINASES - THE CGMP-AND CAMP-DEPENDENT PROTEIN-KINASES

The cAMP-dependent (PKA) and cGMP-dependent protein kinases (PKG) shar e a strong primary sequence homology within their respective active si te regions. Not surprisingly, these enzymes also exhibit overlapping s ubstrate specificities, a feature that often interferes with efforts t o elucidate their distinct biological roles. In this report, we demons trate that PKA and PKG exhibit dramatically different behavior with re spect to the phosphorylation of alpha-substituted alcohols. Although P KA will phosphorylate only residues that contain an alpha-center confi guration analogous to that found in L-serine, PKG utilizes residues th at correspond to both L- and D-serine as substrates. The PKG/PKA selec tivity of these substrates is the highest ever reported.