Fig. 4

Regulation of insulin-like growth factor (IGF) transport and uptake by insulin-like growth factor binding proteins (IGFBPs) pathway. The pathway consists of several networks: IGFBP1 binds with IGF, forming IGF:IGFBP1; IGFBP2 binds with IGF, forming IGF:IGFBP2; IGFBP4 binds with IGF, forming IGF:IGFBP4; IGFBP6 binds with IGF, forming IGF:IGFBP6; PAAP-A proteolyzes IGF:IGFBP4; FAM20C phosphorylates FAM20C substrates. IGF-I binds to its receptor (IGF-IR), which leads to IRS/PI3K phosphorylation and subsequent downstream activation of AKT. Alternatively, IGF-I can activate Shc/Grb-2/Sos phosphorylation and complex formation. This event promotes the activation of the Ras/Raf/MEK/MAPK cascade. IGF-I binds to the hybrid IGF-IR/IR receptor, activating PI3K and MAPK pathways. The IGF-II/IGF-IIR complex can activate an alternative pathway that is associated with the G protein and phospholipase C (PLC). The result of the PLC activity is the production of diacylglycerol (DAG) and inositol triphosphate (IP3), which in turn can activate protein kinase C (PKC) and the RAF/MEK/ERK pathway. IGF-I also binds with IGF-IIR, and IGF-II also binds with IGF-IR. It not well-known which pathways are activated following these interactions. IGFBP proteins bind with either IGF-I or IGF-II and modulate their activities