Regional distribution of calcium- and cyclic adenosine 3':5'-monophosphate-regulated protein phosphorylation systems in mammalian brain. I. Particulate systems.

The regional distribution of phosphoproteins whose phosphorylation is regulated either by cyclic AMP or by calcium in combination with calmodulin or phospholipid has been investigated in particulate preparations from rat CNS. About 30 distinct phosphoproteins were observed. These phosphoproteins exhibited widely different patterns of regional distribution. Based upon distribution patterns, we have divided these phosphoproteins into three categories: category A, phosphoproteins found in all parts of the CNS in approximately equal amounts; category B, phosphoproteins which are widely distributed within the CNS but show large regional variations; and category C, phosphoproteins which show a highly restricted regional distribution. We have tentatively interpreted the results on particulate phosphoproteins in the following way: some are present in all or nearly all brain cells, others are present only in certain classes of brain cells, and still others have an even more limited distribution, being present in only a single type of brain cell. The regional distribution of particulate protein kinase activity was also examined. Calcium/calmodulin-dependent protein kinase activity had a marked regional distribution, whereas cyclic AMP-dependent protein kinase activity was more evenly distributed. Calcium/phospholipid-dependent protein kinase activity was barely detectable under the experimental conditions used. This investigation thus demonstrates striking differences in the regional distribution of particulate protein phosphorylation systems in mammalian brain. These regional differences may reflect highly specific functional roles for certain of these protein phosphorylation systems. Similar conclusions concerning cytosolic protein phosphorylation systems are described in the accompanying paper.