IGFBP3
Description
The IGFBP3 (insulin like growth factor binding protein 3) is a protein-coding gene located on chromosome 7.
Insulin-like growth factor-binding protein 3, also known as IGFBP-3, is a protein encoded by the IGFBP3 gene in humans. It is one of six IGF binding proteins (IGFBP-1 to IGFBP-6) that share highly conserved structures and bind the insulin-like growth factors IGF-1 and IGF-2 with high affinity. IGFBP-7, sometimes considered part of this family, lacks the conserved structural features and high IGF affinity. Instead, it binds IGF1R, which blocks IGF-1 and IGF-2 binding, leading to apoptosis.
IGFBP-3 was first identified, characterized, and quantified in human plasma in 1986. It plays significant roles in the circulation, extracellular environment, and within cells. In the bloodstream, it serves as the main IGF transport protein, carrying the growth factors primarily in stable complexes containing the binding protein, either IGF-1 or IGF-2, and a third protein called the acid-labile subunit or ALS.
For IGFs to reach tissues from the bloodstream, the circulating complexes are believed to partially dissociate, potentially facilitated by limited proteolysis of IGFBP-3. The IGF-1/IGFBP-3 ratio has sometimes been used as a measure of IGF bioavailability in the circulation, but this approach ignores IGF-1 binding to other IGFBPs, making the ratio dependent on the concentrations of all six IGFBPs. Moreover, it overlooks the fact that IGF-2, which is three times more abundant than IGF-1 in the bloodstream of adults, occupies most of the binding sites on circulating IGFBP-3.
Within tissues, IGFBP-3 can bind IGF-1 and IGF-2 released by various cell types, blocking their access to the IGF-1 receptor (IGF1R), which is activated by both IGFs. IGFBP-3 also interacts with cell-surface proteins, influencing cell signaling from outside the cell or after internalization. It can also enter the cell nucleus, where it binds to nuclear hormone receptors and other ligands.
IGF-binding proteins, including IGFBP-3, extend the lifespan of IGFs and can either hinder or encourage the growth-promoting effects of IGFs in cell cultures. They modify the interaction of IGFs with their cell surface receptors. IGFBP-3 also displays IGF-independent anti-proliferative and apoptotic effects through its receptor TMEM219/IGFBP-3R. It suppresses the positive influence of humanin on insulin sensitivity (PubMed:19623253) and promotes testicular germ cell apoptosis (PubMed:19952275). (ECO:0000269|PubMed:19623253, ECO:0000269|PubMed:19952275, ECO:0000269|PubMed:20353938).
IGFBP3 is also known as BP-53, IBP-3, IBP3, IGFBP-3.
