Protein kinase B/Akt modulators and methods for the use thereof

A method for identifying a compound that disrupts the interaction between an inhibitor of PKB/Akt protein and a PKB/Akt protein, said method comprising:

• contacting said inhibitor and said PKB/Akt protein in the presence and absence of a test compound, and
• determining whether said test compound decreases the level of complex formation between said inhibitor and said PKB/Akt protein, relative to the level of complex formation in the absence of said test compound,
• thereby identifying a compound that disrupts said interaction:
• wherein said inhibitor of PKB/Akt protein is a Tribbles (TRB) family protein selected from the group consisting of human TRB-3 having the sequence set forth in SEQ ID NO:1, mouse TRB-3 having the sequence set forth in SEQ ID NO:2, rat TRB-3 having the sequence set forth in SEQ ID NO:3, C5FW having the sequence set forth in SEQ ID NO:4, C8FW having the sequence set forth in SEQ ID NO:5, Drosophila Tribbles protein having the sequence set forth in SEQ ID NO:6, TRB-1 having the sequence set forth in SEQ ID NO:7, and TRB-2 having the sequence set forth in SEQ ID NO:8.

A method for screening test compounds to determine if any affect the phosphorylation state of a mammalian protein kinase B (PKB)/Akt protein kinase, said method comprising:

• assaying for the phosphorylation level of said PKB/Akt protein in the presence of an inhibitor of PKB/Akt protein and a test compound relative to the phosphorylation level of said PKB/Akt protein in the presence of said modulator alone;
• wherein said inhibitor of PKB/Akt protein is a Tribbles (TRB) family protein selected from the group consisting of human TRB-3 having the sequence set forth in SEQ ID NO:1, mouse TRB-3 having the sequence set forth in SEQ ID NO:2, rat TRB-3 having the sequence set forth in SEQ ID NO:3, C5FW having the sequence set forth in SEQ ID NO:4, C8FW having the sequence set forth in SEQ ID NO:5, Drosophila Tribbles protein having the sequence set forth in SEQ ID NO:6, TRB-1 having the sequence set forth in SEQ ID NO:7, and TRB-2 having the sequence set forth in SEQ ID NO:8;
• and
• wherein a change in said phosphorylation level is indicative of a compound which affects the phosphorylation state of said PKB/Akt protein.