Protein kinase C activation by phorbol esters: do cysteine-rich regions and pseudosubstrate motifs play a role?
A model for the binding of two activators of protein kinase C (PKC), the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and diacylglycerol, to the enzyme is proposed. It is suggested that each activator is hydrogen-bonded to sulfhydryl groups of cysteine residues and to the carbonyl of an asparagine within the cysteine-rich regions of PKC. This might induce a conformational change that would disrupt the association of the inhibitory pseudosubstrate sequence with the active center of PKC.
Gschwendt
M
M
German Cancer Research Center, Institute of Biochemistry, Heidelberg.
Kittstein
W
W
Marks
F
F
D000595:Amino Acid Sequence; D003545:Cysteine / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism; D004789:Enzyme Activation; D006860:Hydrogen Bonding; D008956:Models, Chemical; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism*
D004075:Diglycerides; D013438:Sulfhydryl Compounds; D011493:Protein Kinase C; D003545:Cysteine; D013755:Tetradecanoylphorbol Acetate