METHOD FOR SCREENING FOR SUBSTANCES WHICH ARE ACTIVATORS, INHIBITORS OR BINDERS OF PKB BY THE USE OF A SUBSTRATE PEPTIDE AND THE USE OF THE SUBSTRATE PEPTIDE

摘要

The invention relates to a method for screening for substances which are activators or inhibitors of Protein kinase B (PKB) and can be used as a kina se substrate for PKB. The substrate is a peptide comprising the two sequences R -R- R-A-A/V-S-M and R-P/S-R-S/T-S/N-S-N and preferably comprising the three sequences R-P-R-S-C-T-W, R-R-R-A-A/V-S-M and R-P/S-R-S/T-S/N-S-N. These sequences as well as the human Afx, amino acids 12-505 or amino acids 1-505, can be used in assays measuring the activity of PKB, and in screening for substances which are activators or inhibitors of gene transcriptional regulation of forkhead proteins through the catalytic activities of PKB. The se sequences can also be used for discrimination between the effects of compoun ds which mediate insulin action through transcription from those which modulate activity of enzymes involved in metabolism by phosphorylation.