Development of an antagonist of PKC epsilon-induced signal transduction

Protein kinase C (PKC) is a family of 10 isozymes, which are involved in the intracellular signal transduction. The different PKC isozymes are interesting targets for the treatment of different diseases such as allergy, asthma, arthritis, AIDS, multiple sclerosis, high blood pressure, cardiac hypertrophy, arteriosclerosis, diabetes, alcoholism and tumors. The exact functions if the different PKC isozymes are not known at present. In this project it is intended to investigate PKC epsilon. It was shown previously that this isozyme is an congene, causes cardiac hypertrophy and increases alcohol consumption. Following activation of PKC epsilon, it binds to RACK2 to transduce signals. It was shown that a peptide derived from PKC epsilon inhibits the binding to RACK2 and inhibits PKC epsilon-induced signal transduction. In this project it is planned, to employ this peptide for molecular modelling (computer simulation of molecules), in order to find chemical compounds (peptidomimetics), which imitate the action of this peptide. These compounds will be synthesized and tested for their ability to inhibit PKC epsilon-induced signal transduction. Such compounds might be useful for treatment of tumors, cardiac hypertrophy or alcoholism.

Protein kinase C (PKC) is a family of 10 isozymes, which are involved in the intracellular signal transduction. The different PKC isozymes are interesting targets for the treatment of different diseases such as allergy, asthma, arthritis, AIDS, multiple sclerosis, high blood pressure, cardiac hypertrophy, arteriosclerosis, diabetes, alcoholism and tumors. The exact functions if the different PKC isozymes are not known at present. In this project it is intended to investigate PKC epsilon. It was shown previously that this isozyme is an congene, causes cardiac hypertrophy and increases alcohol consumption. Following activation of PKC epsilon, it binds to RACK2 to transduce signals. It was shown that a peptide derived from PKC epsilon inhibits the binding to RACK2 and inhibits PKC epsilon-induced signal transduction. In this project it is planned, to employ this peptide for molecular modelling (computer simulation of molecules), in order to find chemical compounds (peptidomimetics), which imitate the action of this peptide. These compounds will be synthesized and tested for their ability to inhibit PKC epsilon-induced signal transduction. Such compounds might be useful for treatment of tumors, cardiac hypertrophy or alcoholism.