PMID- 18704375
OWN - NLM
STAT- MEDLINE
DCOM- 20081222
LR  - 20161124
IS  - 1618-2650 (Electronic)
IS  - 1618-2642 (Linking)
VI  - 392
IP  - 6
DP  - 2008 Nov
TI  - Phosphorylation of xenobiotic-metabolizing cytochromes P450.
PG  - 1085-92
LID - 10.1007/s00216-008-2315-2 [doi]
AB  - The regulation of cytochromes P450 (CYPs) by induction mediated by xenobiotics is 
      well known. Our team has discovered an additional important regulation of 
      xenobiotic-metabolizing CYPs by phosphorylation. Individual CYPs are 
      phosphorylated by different protein kinases, leading to CYP isoenzyme-selective 
      changes in the metabolism of individual substrates and consequent profound 
      changes in the control of mutagenic and cytotoxic metabolites. Some CYPs are 
      phosphorylated by protein kinase C and some by the cyclic adenosine monophosphate 
      (cAMP) dependent protein kinase A. We found that cAMP not only leads to drastic 
      changes in the activity of individual CYPs, but also drastic changes in the 
      nuclear localization of the CYP-related transcription factor Ah receptor (AHR). 
      The consequences are very different from those of AHR nuclear translocation 
      mediated by its classic ligands (such as dioxin and many polycyclic aromatic 
      hydrocarbons) and may represent the long-sought physiological function of the 
      AHR. The disturbance of this physiological function of AHR by extremely 
      persistent high-affinity xenobiotic ligands such as dioxin may represent the most 
      important contributing factor for their potent toxicity.
FAU - Oesch-Bartlomowicz, B
AU  - Oesch-Bartlomowicz B
AD  - ECNIS Section, Johannes Gutenberg University, 55131, Mainz, Germany. 
      oeschb@uni-mainz.de
FAU - Oesch, F
AU  - Oesch F
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20080814
PL  - Germany
TA  - Anal Bioanal Chem
JT  - Analytical and bioanalytical chemistry
JID - 101134327
RN  - 0 (Dioxins)
RN  - 0 (Ligands)
RN  - 0 (Polycyclic Aromatic Hydrocarbons)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Xenobiotics)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Cyclic AMP/metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - Cytochrome P-450 Enzyme System/*metabolism
MH  - Dioxins/metabolism
MH  - Ligands
MH  - Phosphorylation
MH  - Polycyclic Aromatic Hydrocarbons/metabolism
MH  - Protein Kinase C/metabolism
MH  - Receptors, Aryl Hydrocarbon/*metabolism
MH  - Receptors, Cytoplasmic and Nuclear/*metabolism
MH  - Xenobiotics/*metabolism
RF  - 53
EDAT- 2008/08/16 09:00
MHDA- 2008/12/23 09:00
CRDT- 2008/08/16 09:00
PHST- 2008/04/14 00:00 [received]
PHST- 2008/07/23 00:00 [accepted]
PHST- 2008/07/22 00:00 [revised]
PHST- 2008/08/16 09:00 [pubmed]
PHST- 2008/12/23 09:00 [medline]
PHST- 2008/08/16 09:00 [entrez]
AID - 10.1007/s00216-008-2315-2 [doi]
PST - ppublish
SO  - Anal Bioanal Chem. 2008 Nov;392(6):1085-92. doi: 10.1007/s00216-008-2315-2. Epub 
      2008 Aug 14.