An ATP-Site On-Off Switch That Restricts Phosphatase Accessibility of Akt

Kui Lin,* Jie Lin, Wen-I Wu, Joshua Ballard, Brian B. Lee, Susan L. Gloor, Guy P. A. Vigers, Tony H. Morales, Lori S. Friedman, Nicholas Skelton, Barbara J. Brandhuber*

*To whom correspondence should be addressed. E-mail: klin{at}gene.com (K.L.); bbrandhuber{at}arraybiopharma.com (B.J.B.)

This PDF file includes:

• Fig. S1. Structures of Akt inhibitors used in this study.
• Fig. S2. The activity of PP2A or PP1 is inhibited by ATP, ADP, and AMP-PNP, but not by Akt inhibitors.
• Fig. S3. ATP-competitive inhibitors block dephosphorylation of Akt2 and Akt3.
• Fig. S4. ATP-competitive inhibitors block dephosphorylation of Akt by PP1.
• Fig. S5. Scenarios to explain the phosphorylation status of Akt in cells treated with upstream kinase inhibitors before or after treatment with the ATP-competitive inhibitors.
• Table S1. Data collection and refinement statistics.
• Table S2. Akt1 residues within 4 Å of GDC-0068.
• Table S3. LanthaScreen displacement binding assay results.
• Table S4. Quantification and statistical analysis of Western blotting data.
  

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© 2012 American Association for the Advancement of Science