Cyclic GMP-dependent protein phosphorylation in mammalian brain

Many of the actions of cyclic AMP (cAMP) and cyclic GMP (cGMP) are believed to be mediated via the phosphorylation of specific substrate proteins by cAMP-dependent and cGMP-dependent protein kinases. cGMP-regulated protein phosphorylation systems are less widely distributed than cAMP-regulated systems. This conclusion is supported by studies of the distribution, within the mammalian brain, of cGMP-dependent protein kinase and of G substrate, the only specific substrate protein for this enzyme yet found in the nervous system. cGMP-dependent protein kinase and G substrate are both highly enriched in the cerebellum. Within the cerebellum both proteins are concentrated in Purkinje cells. The localization of these and other components of the cGMP-dependent protein phosphorylation system in Purkinje cells suggests an important and selective role for cGMP in this neuron. The functional significance of cGMP-dependent protein kinase and G substrate in the Purkinje cell is currently being investigated. That study should be greatly facilitated by the recent preparation and characterization of serum antibodies highly selective for either the phospho or dephospho form of G substrate.