Specific inhibition of AGC protein kinases by antibodies against C-terminal epitopes.
The sequences contributing to the catalytic site of protein kinases are not all comprised within the highly conserved catalytic core. Thus, in mammalian cAMP-dependent protein kinase (PKA), the C-terminal sequence participates in substrate binding. Using synthetic peptides mimicking the FxxF motif present at most C-termini of AGC kinases, we have raised highly specific antibodies which are potent and specific inhibitors of the catalytic activity of the cognate protein kinase. Taking into account the structure of PKA, these results point to the potential of the C-terminal region of protein kinases as a target for designing specific protein kinase inhibitors.
Unité de Régulation Enzymatique des Activités Cellulaires, CNRS URA 2185, Institut Pasteur, 25-28 rue du Dr Roux, 75724 Paris Cedex 15, France. traincar@pasteur.fr
François
F
Traincard
Véronique
V
Giacomoni
Michel
M
Veron
D000595:Amino Acid Sequence; D000818:Animals; D001666:Binding Sites, Antibody; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D000939:Epitopes / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D000939:Epitopes; D010446:Peptide Fragments; D017868:Cyclic AMP-Dependent Protein Kinases