Skeletal muscle sarcolemma proteins as targets for adenosine 3':5'-monophosphate-dependent and calcium-dependent protein kinases.

The present study documents the existence in rat skeletal muscle plasma membrane (sarcolemma) of a distinct set of proteins, most of which represent unknown protein species, which can be phosphorylated in vitro by addition of cAMP-dependent or calcium-dependent protein kinases. Under the experimental conditions used, cAMP-regulated protein phosphorylation appeared to be the most important phosphorylation system in these membranes, followed by the calcium/phospholipid-regulated, and, with only a few substrates detected, the calcium/calmodulin-regulated systems. No specific substrate for cGMP-dependent protein kinase was found. In contrast, calcium/calmodulin-regulated protein phosphorylation was the most important in the sarcoplasmic reticulum fraction. Most of the cAMP-regulated and calcium/phospholipid-regulated sarcolemma phosphoproteins appeared to be intrinsic membrane proteins, at least three of which appeared to be phosphorylated by both these protein kinases. These phosphoproteins may represent membrane targets for multiple hormone or transmitter actions in skeletal muscle cells. Our results, therefore, suggest that protein phosphorylation systems, particularly those regulated by cAMP or calcium/phospholipid, may be more important in the regulation of sarcolemma function than hitherto believed.