Tryptophan hydroxylase is phosphorylated by protein kinase A.
The effect of protein kinase A on the catalytic activity and phosphorylation of brain tryptophan hydroxylase was examined. Stimulation of endogenous protein kinase A by cyclic AMP or its analogues, dibutyryl-cyclic AMP and 8-thiomethyl-cyclic AMP, failed to activate tryptophan hydroxylase. The activation of tryptophan hydroxylase by calcium/calmodulin-phosphorylating conditions was not modified by cyclic AMP. Endogenous protein kinase A phosphorylated a large number of proteins and tryptophan hydroxylase could be identified as one substrate by sucrose gradient centrifugation, immunoprecipitation, and immunoblotting. These results indicate that tryptophan hydroxylase is phosphorylated by protein kinase A in brain and question whether this protein kinase exerts direct regulatory influence over tryptophan hydroxylase activity via phosphorylation.
Johansen
P A
PA
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan, USA.
Jennings
I
I
Cotton
R G
RG
Kuhn
D M
DM
D000818:Animals; D001345:Autoradiography; D002499:Centrifugation, Density Gradient; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D015151:Immunoblotting; D008297:Male; D010750:Phosphoproteins / Q000096:biosynthesis; D010766:Phosphorylation; D011233:Precipitin Tests; D051381:Rats; D014365:Tryptophan Hydroxylase / Q000378:metabolism*
D010750:Phosphoproteins; D000242:Cyclic AMP; D014365:Tryptophan Hydroxylase; D017868:Cyclic AMP-Dependent Protein Kinases