Figure 7

Proposed pathway.

In this model, IGF-I peptide binds to IGF-IR to induce tyrosine autophosphorylation and phosphorylation of its adaptor protein Shc. Phosphorylated Shc then is associated with the Grb2-mSOS complex to activate p21/Ras, which leads to proliferation by activation of the Ras/Raf/MAPK pathway. The IGF-I and IGF-IR complex also autophosphorylates its docking protein IRS-I, which, in turn, activates the survival PI3K/AKT pathway. However, on the basis of our studies, this pathway appears not to be playing a major role in leiomyoma growth. IRS-I also may recruit Grb2, but it appears that the Shc-Grb2 pathway is the predominant activator of p21/Ras in IGF-IR signaling in UtLM cells and uterine leiomyoma tissue.