PROTEIN-KINASE-C PHOSPHORYLATES AND ACTIVATES GTP CYCLOHYDROLASE-I INRAT RENAL MESANGIAL CELLS

GTP cyclohydrolase I is the rate-limiting enzyme in the de novo synthe sis pathway of tetrahydrobiopterin which is an essential cofactor for all NO synthase isoforms. The expression of GTP cyclohydrolase I is re gulated on a transcriptional level by a variety of cytokines like inte rleukin 1 beta or tumor necrosis factor a. The present paper reports t hat stimulation of protein kinase C by angiotensin II, platelet-derive d growth factor BE or the phorbol ester 12-O-tetradecanoylphorbol-13-a cetate triggers the phosphorylation and activation of GTP cyclohydrola se I. These data establish that in addition to transcriptional regulat ion, there is a prominent posttranscriptional modulation of enzyme act ivity. (C) 1998 Academic Press.