Table 1.
The IGF System Complex⁎
| IGF ligands | IGF receptors | IGF-binding proteins | Main effectors |
|---|---|---|---|
| Insulin | Insulin receptor | IGFBP1-IGFBP6 | IRS-1 |
| IGF-1 | IGF-1 receptors A and B | IGFBP-related proteins | JCV-T |
| IGF-2 | IGF-2/mannose-6-phosphate receptor | IGFBP proteases | MAPKs |
| Insulin receptor–related receptor | PI3K/Akt | ||
| Insulin/IGF-1 hybrid receptor | |||
| ALS |
IGF, insulin-like growth factor; IGFBP, IGF-binding protein; IRS, insulin receptor substrate; JCV-T, human polyomavirus JCV protein T; MAPK, mitogen-activated protein kinase; PI3K, phosphatidylinositol 3-kinase; Akt, antiapoptotic protein family; ALS, acid-labile subunit.
The IGF-1 binds to IGFBP-3 in a 1:1 molar ratio. Other IGFBPs are inhibitory. For example, both IGFBP-2 and IGFBP-5 have a greater affinity for IGF-1 than the receptor. Therefore, increases in serum levels of these two IGFBPs result in a decrease in IGF-1 activity and vice versa. The ALS acts in the IGFs by binding circulating IGF-1 in a ternary complex together with binding protein IGFBP-3: ALS may influence skin carcinogenesis by modulating IGF-1 levels or its bioavailability. In addition, high circulating ALS levels reduce the concentration of free IGF-1 in circulation.