Posttranslational Modification of Cytochrome P450

  • I. Jansson
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 105)


After the actual biosynthesis of the cytochrome P450 proteins some of them may be further modified before they become functionally active proteins. Protein phosphorylation has come to be recognized as the most common type of posttranslational reversible protein modification in eukaryotic organisms (Krebs 1986). Many different types of protein kinases exist capable of phosphorylating many different protein substrates. Different protein kinases can also phosphorylate the same protein substrate, often with the same amino acid being phosphorylated. A unifying scheme for cellular metabolism by protein phosphorylation is that catabolism is activated by protein phosphorylation while anabolic processes are promoted by protein dephosphorylation (Shenolikar 1988). A number of different regulatory protein kinases exist. One of these, the cyclic AMP-dependent protein kinase, is a highly specific enzyme. Out of a large number of serine or threonine residues that are available, physiological substrates are only phosphorylated at one or two sites (Cohen 1982). These physiological substrates invariably contain two adjacent basic amino acids just N-terminal to the residue that is phosphorylated, ARG-ARG-X-SER as the substrate recognition sequence. This protein kinase exists as an inactive holoenzyme consisting of two catalytic and two regulatory subunits, which, upon binding of cAMP to this complex, dissociates releasing the active catalytic subunit (Krebs and Beavo 1979).


Microsomal Cytochrome Monooxygenase Activity Calmodulin Antagonist Cytochrome P450 Protein Bovine Adrenocortical Cell 
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  • I. Jansson

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