Competitive inhibitors and allosteric activators of protein kinase C isoenzymes: a personal account and progress report on transferring academic discoveries to the clinic.
PKC (protein kinase C) isoenzymes are related protein kinases, involved in many signalling events in normal state and in disease. Basic research into identifying the molecular basis of PKC selectivity led to simple strategies to identify selective competitive inhibitor peptides and allosteric agonist peptides of individual PKC isoenzymes. The strategies and rationale used to identify these peptide regulators of protein-protein interaction may be applicable to other signalling events. Importantly, the PKC-regulating peptides proved to be useful pharmacological tools and may serve as drugs or drug leads for a variety of human diseases.
Budas
G R
GR
Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305-5174, U.S.A.
Koyanagi
T
T
Churchill
E N
EN
Mochly-Rosen
D
D
D000595:Amino Acid Sequence; D020536:Enzyme Activators / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000201:enzymology
D020536:Enzyme Activators; D007527:Isoenzymes; D047428:Protein Kinase Inhibitors; D011493:Protein Kinase C