Precision substrate targeting of protein kinases. The cGMP- and cAMP-dependent protein kinases.
The cAMP-dependent (PKA) and cGMP-dependent protein kinases (PKG) share a strong primary sequence homology within their respective active site regions. Not surprisingly, these enzymes also exhibit overlapping substrate specificities, a feature that often interferes with efforts to elucidate their distinct biological roles. In this report, we demonstrate that PKA and PKG exhibit dramatically different behavior with respect to the phosphorylation of alpha-substituted alcohols. Although PKA will phosphorylate only residues that contain an alpha-center configuration analogous to that found in L-serine, PKG utilizes residues that correspond to both L- and D-serine as substrates. The PKG/PKA selectivity of these substrates is the highest ever reported.
Department of Chemistry, State University of New York, Buffalo 14260, USA.
J S
JS
Wood
X
X
Yan
M
M
Mendelow
J D
JD
Corbin
S H
SH
Francis
D S
DS
Lawrence
D000595:Amino Acid Sequence; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D010766:Phosphorylation; D013237:Stereoisomerism; D013379:Substrate Specificity
D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases