IRS-1: Auditing the effectiveness of mTOR inhibitors John B. Easton, Raushan T. Kurmasheva, Peter J. Houghton  Cancer Cell  Volume 9, Issue 3, Pages 153-155 (March 2006) DOI: 10.1016/j.ccr.2006.02.027 Copyright © 2006 Elsevier Inc. Terms and Conditions

Figure 1 Self-regulation of the IGF-I signaling pathway Ligand binding induces IGF-IR phosphorylation and association of IRS-1, which in turn is phosphorylated on multiple sites, resulting in the recruitment of the p110 catalytic subunit of PI3K. Akt phosphorylates and inhibits the function of TSC2, thus relieving the negative constraints on Rheb, leading to mTOR activation. Phosphorylation of S6K1 by mTOR leads to phosphorylation of IRS-1 and its degradation via the proteasome (broken red arrow). A second feedback loop that senses inhibition of translation activates mTOR, leading to phosphorylation of ribosomal protein S6 (broken red arrow). Cancer Cell 2006 9, 153-155DOI: (10.1016/j.ccr.2006.02.027) Copyright © 2006 Elsevier Inc. Terms and Conditions