Fig. 7. A model for IGFBP regulation of apoptosis. IGFBP-5 is secreted from the basal surface of mammary epithelial cells where it is suitably placed to interact with IGFs. This interaction prevents IGF-mediated activation of the type I IGF receptor (IGF-IR) and inhibits (-) phosphorylation of insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB). In the inactive state, PKB is unable to phosphorylate downstream effectors such as forkhead transcription factors (e.g. FKHRL1) leading to FKHRL1 activation (+), induction of apoptosis and subsequently, involution.