PHOSPHORYLATION AND ACTIVATION OF CGMP-DEPENDENT PROTEIN-KINASE BY SRC

Using information obtained from experiments with peptide substrates of v-Src, a motif within the cGMP-binding domain of cGMP-dependent prote in kinase (cGK) was identified as a potential phosphorylation site for v-Src. Here we show that the purified I alpha isozyme of cGK is phosp horylated stoichiometrically and in a time-dependent manner by purifie d Src in vitro. The kinase activity of cGK is elevated approximately 4 -fold (relative to autophosphorylated cGK) or 10-fold (relative to unp hosphorylated cGK) upon tyrosine phosphorylation by Src. Phosphorylati on of cGK by v-Src produces modest effects on the cGMP-binding propert ies and dissociation rates of cGK, and reduces the k(act) for cGMP. We hypothesize that the mechanism of activation may involve coupling of the cGMP binding domain to the catalytic domain. (C) 1998 Elsevier Sci ence B.V. All rights reserved.