IGFII

IGF-II, or insulin-like growth factor II, is a peptide growth factor in the insulin-like growth factor family. It shares structural similarity with insulin and plays a key role in growth and development, particularly during fetal life. IGF-II is produced as a precursor protein and is processed to mature IGF-II, with additional larger “pro” or “big” isoforms in some contexts.

The IGF2 gene, located on chromosome 11p15.5 in humans, encodes IGF-II. The gene uses multiple promoters to generate various transcripts, which are then translated into precursor proteins and processed to the bioactive peptide. IGF-II is widely expressed in fetal tissues, with expression levels generally higher before birth and decreasing after birth, though it remains present at lower levels in many tissues.

IGF-II signals primarily through the IGF1 receptor (IGF1R), activating downstream pathways such as PI3K-AKT and MAPK that promote cell growth, survival, and metabolism. IGF-II can also interact with the insulin receptor isoform IR-A, though with lower affinity. A second receptor, IGF2R (also known as the cation-independent mannose-6-phosphate receptor), binds IGF-II to regulate its clearance and does not typically promote signaling for growth. IGF-binding proteins (IGFBPs) modulate IGF-II availability and activity.

Genomic imprinting tightly regulates IGF2 expression: in many tissues, IGF2 is expressed from the paternal allele while the maternal allele is silenced. Dysregulation of this imprinting or overexpression of IGF-II is associated with growth disorders such as Beckwith-Wiedemann syndrome and with various cancers, where loss of imprinting or increased IGF-II signaling can contribute to tumor growth. IGF-II remains a focus of research for developmental biology and targeted cancer therapies.