Protein kinase C-dependent phosphorylation and mitochondrial translocation of aldose reductase.
Although aldose reductase (AR) is a critical participant in osmoregulation, and the metabolism of glucose and aldehydes derived from lipid peroxidation, post-translational mechanisms regulating its activity have not been identified. In this paper, we report that stimulation of protein kinase C (PKC) in several cell types induces phosphorylation of AR and translocation of the phosphorylated protein to the mitochondria. In vitro, recombinant AR was directly phosphorylated by activated PKC, suggesting that AR may be an in vivo PKC substrate. Together, these observations reveal a novel link between PKC activation and the regulation of glucose and aldehyde metabolism.
Varma
Tushar
T
Division of Anesthesiology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77550, USA.
Liu
Si Qi
SQ
West
Matthew
M
Thongboonkerd
Visith
V
Ruvolo
Peter P
PP
May
W Stratford
WS
Bhatnagar
Aruni
A
D000449:Aldehyde Reductase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D054713:Bryostatins; D019556:COS Cells; D002478:Cells, Cultured; D018922:HL-60 Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology; D018942:Macrolides; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D054713:Bryostatins; D007783:Lactones; D018942:Macrolides; D010761:Phosphorus Radioisotopes; D011994:Recombinant Proteins; C046785:bryostatin 1; D000449:Aldehyde Reductase; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate