IGFBP3

IGFBP-3, or insulin-like growth factor binding protein 3, is a secreted protein encoded by the IGFBP3 gene in humans. It is the most abundant IGF binding protein in circulation and is a member of the IGFBP family that regulates the activity of insulin-like growth factors I and II.

IGFBP-3 binds IGF-I and IGF-II with high affinity, modulating their bioavailability and biological effects. In the bloodstream, most IGF is carried in a ternary complex composed of IGF, IGFBP-3, and the acid-labile subunit (ALS). This complex prolongs IGF half-life and controls access to the IGF receptors, thereby shaping IGF signaling in tissues.

Beyond its IGF-dependent actions, IGFBP-3 can exert IGF-independent effects. It can influence cell growth, differentiation, and apoptosis through interactions with cellular receptors and intracellular pathways, including potential nuclear actions that affect gene expression. IGFBP-3 can be internalized and translocated to the nucleus, where it may participate in pro-apoptotic signaling under certain conditions. Proteolytic cleavage of IGFBP-3 by proteases reduces IGF binding and can alter its functional properties.

IGFBP-3 is mainly produced by the liver, and its expression is stimulated by growth hormone. It is also regulated by other factors, including p53, glucocorticoids, and nutritional status. Circulating levels of IGFBP-3, together with IGF-1, are used in clinical settings to assess growth hormone status and to study various disease states.

In research and clinical contexts, IGFBP-3 is studied as a potential biomarker and therapeutic target due to its central role in modulating IGF signaling and its IGF-independent activities in cell fate regulation.