Protein kinase C phosphorylates and regulates UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase.
UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (UDP-GlcNAc 2-epimerase) is the key enzyme in the de novo synthesis pathway of neuraminic acid, which is widely expressed as a terminal carbohydrate residue on glycoconjugates. UDP-GlcNAc 2-epimerase is a bifunctional enzyme and catalyzes the first two steps of neuraminic acid synthesis in the cytosol, the conversion of UDP-N-acetylglucosamine to ManAc and the phosphorylation to ManAc-6-phosphate. So far, regulation of this essential enzyme by posttranslational modification has not been shown. Since UDP-N-acetylglucosamine is a cytosolic protein containing eight conserved motifs for protein kinase C (PKC), we investigated whether its enzymatic activity might be regulated by phosphorylation by PKC. We showed that UDP-GlcNAc 2-epimerase interacts with several isoforms of PKC in mouse liver and is phosphorylated in vivo. Furthermore, PKC phosphorylates UDP-GlcNAc 2-epimerase and this phosphorylation results in an upregulation of the UDP-GlcNAc 2-epimerase enzyme activity.
Horstkorte
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Institut für Molekularbiologie und Biochemie, Freie Universität Berlin, Arnimallee 22, D-14195, Berlin-Dahlem, Germany. rhorstko@zedat.fu-berlin.de
Nöhring
S
S
Danker
K
K
Effertz
K
K
Reutter
W
W
Lucka
L
L
D020816:Amino Acid Motifs; D000818:Animals; D002238:Carbohydrate Epimerases / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D016384:Consensus Sequence; D004789:Enzyme Activation / Q000187:drug effects; D029968:Escherichia coli Proteins; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism; D009438:Neuraminic Acids / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D018411:Spodoptera; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D029968:Escherichia coli Proteins; D007527:Isoenzymes; D009097:Multienzyme Complexes; D009438:Neuraminic Acids; D011994:Recombinant Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C018765:N-acylmannosamine kinase; D011493:Protein Kinase C; D002238:Carbohydrate Epimerases; C100033:UDP acetylglucosamine-2-epimerase; C083982:wecB protein, E coli; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate