Fig. 1. Insulin-like growth factor 1 (IGF-1)-mediated signaling pathways relevant to hypertrophy. Binding of IGF-1 activates the IGF-1 receptor (purple), which then recruits insulin-receptor substrate (IRS-1). This leads to the activation of two signaling pathways: the Ras–Raf–MEK–ERK pathway and the phosphatidylinositol 3-kinase (PI3K)– Akt pathway. The PI3K–Akt pathway recapitulates hypertrophy caused by IGF-1 stimulation. Akt1 activity can be modulated either by directly controlling its phosphorylation state or by altering the levels of the lipid that it binds at the cell membrane, phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3] (orange). Signaling molecules that have been shown to have a negative effect on hypertrophy are colored red, and proteins whose activation induces hypertrophy are shown in green. Proteins that have not been assayed for their role in hypertrophy are shown in blue. Abbreviations: eIF-2B, eukaryotic translation initiation factor 2B; ERK, extracellular-signal-regulated kinase; GSK3b, glycogen-synthase kinase 3b; mTOR, mammalian target of rapamycin; p70S6K, p70 S6 kinase; PDK, phosphoinositide-dependent protein kinase;