The insulin-like growth factor (IGF) system includes two receptors (IGF-1R and IGF-2R), two ligands (IGF-1 and IGF-2), and seven binding proteins (IGFBP-7). The binding proteins are produced in the liver and bind to the IGFs with different affinities, thus regulating the interaction of the IGFs with their receptors. Insulin-like growth factor binding protein-3 (IGFBP-3) is the major serum carrier protein for IGF proteins. IGFBP-3 sequesters IGF in a stable ternary complex with the acid-labile subunit (ALS). IGFBP-3 binds IGF-1 with high affinity and specificity and modulates IGF-1 action. The high affinity binding site resides within an N-terminal hydrophobic domain in IGFBP-3, but C-terminal residues are also involved. IGFBP-3 also interacts with GAG and heparin. IGFBP-3 undergoes limited enzymatic proteolysis to generate small N-terminal fragments. These proteolytic products lose their affinity for IGF-1 and IGF-2; nevertheless, they preserve IGF independent activity. In that sense, a 16 kD fragment (1-95-IGFBP-3) and the full length molecule can potentiate apoptosis in colorectal epithelial cells, and this apoptotic process is associated with the inhibition of TNF-α-induced NF-kβ activity. Similarly, the N-terminal 1-97-IGFBP-3 fragment induces apoptosis in human prostate cancer cells. In addition, IGFBP-3 has been detected in the cell nucleus and interacts with 9-cis retinoic acid receptor-alpha (RXR-α), a nuclear receptor that is required for the apoptosis-inducing effects of IGFBP-3. It is a death receptor that binds specifically to IGFBP-3 but not other IGFBPs that has been described. IGFBP-3R physically interacts and activates caspase-8 and mediates IGFBP-3-induced apoptosis and tumor suppression.
Size
25 μg
Concentration
n/a
Applications
BA
Other Names
Insulin-like growth factor binding protein 3 (IGFBP3), IBP3, BP-53, BP53