Protein kinase C phosphorylates and activates GTP cyclohydrolase I in rat renal mesangial cells.
GTP cyclohydrolase I is the rate-limiting enzyme in the de novo synthesis pathway of tetrahydrobiopterin which is an essential cofactor for all NO synthase isoforms. The expression of GTP cyclohydrolase I is regulated on a transcriptional level by a variety of cytokines like interleukin 1beta or tumor necrosis factor alpha. The present paper reports that stimulation of protein kinase C by angiotensin II, platelet-derived growth factor BB or the phorbol ester 12-O-tetradecanoylphorbol-13-acetate triggers the phosphorylation and activation of GTP cyclohydrolase I. These data establish that in addition to transcriptional regulation, there is a prominent post-transcriptional modulation of enzyme activity.
Lapize
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C
Zentrum der Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, Frankfurt am Main, D-60590, Germany.
Plüss
C
C
Werner
E R
ER
Huwiler
A
A
Pfeilschifter
J
J
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000918:Antibody Specificity; D000077214:Becaplermin; D004789:Enzyme Activation; D006136:GTP Cyclohydrolase / Q000276:immunology / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000804:Angiotensin II; D000077214:Becaplermin; D011493:Protein Kinase C; D006136:GTP Cyclohydrolase; D013755:Tetradecanoylphorbol Acetate