Activation of hormone-sensitive lipase and phosphorylase kinase by purified cyclic GMP-dependent protein kinase

Abstract

Cyclic[c]GMP-dependent protein kinase, purified to homogeneity from bovein lung, activated hormone-sensitive lipase partially purified from chicken adipose tissue. The degree of activation was the same as that effected by cAMP-dependent protein kinase although higher concentrations of cGMP-dependent enzyme were required (relative activities expressed in terms of histone H2b phosphorylation units). Activation by cAMP-dependent protein kinase was completely blocked by the heat-stable protein kinase inhibitor protein from skeletal muscle but activation by the cGMP-enzyme was not inhibited. Lipase fully activated by cAMP-dependent protein kinase showed no further change in activity when treated with cGMP-dependent protein kinase. Lipase activated by cGMP-dependent protein kinase was reversibly deactivated by purified phosphorylase phosphatase (from bovine heart); full activity was restored by reincubation with cGMP and cGMP-dependent protein kinase. Cholesterol esterase activity in the chicken adipose tissue fraction, previously shown to be activated along with the triglyceride lipase by cAMP-dependent protein kinase, was also activated by cGMP-dependent protein kinase. Crude preparations of hormone-sesnsitive triglyceride lipase from human or rat adipose tissue and cholesterol esterase from rat adrenal were also activated by cGMP-dependent protein kinase. Purified phosphorylase kinase (rabbit skeletal muscle) was also shown to be activated by cGMP-dependent protein kinase. The present results, together with those of other workers on histone phosphorylation, suggest that the substrate specificities of cGMP-dependent and cAMP-dependent protein kinase may be similar. This is discussed in the light of a model recently proposed with regard to the relationship between the subunit structures of the 2 kinases.