STIMULATION OF ADENYLATE-CYCLASE ACTIVITY BY A PROTEASE WHICH ACTIVATES CYCLIC NUCLEOTIDE PHOSPHODIESTERASE

A rat kidney cortex lysosomal protease [Strewler, G. J., Manganiello, V. C. and Vaughan, M. (1977) J. Biol. Chem. 253, 390-394] which activates cyclic nucleotide phosphodiesterases has been shown to potentiate adenylate cyclase activity in normal rat kidney fibroblasts. The lysosomal protease increases GTP-, GTP plus prostaglandin E1-, and guanyl-5′-yl imidodiphosphate-stimulated adenylate cyclase activities by 5-, 2- and 2.8-fold, respectively, but does not significantly enhance the fluoride effect on cyclase activity. Under conditions which lead to maximal protease activation of cyclase activity several plasma membrane proteins are degraded. Of particular interest is the decrease in a 46,000 Mr protein which has been shown to decrease in response to other proteases which activate normal rat kidney fibroblast adenylate cyclase. © 1979.