IGFBP2

What is IGFBP2 protein?

IGFBP2 (insulin like growth factor binding protein 2) is a protein coding gene which situated on the long arm of chromosome 2 at locus 2q35. The protein encoded by this gene is one of six similar proteins that bind insulin-like growth factors I and II (IGF-I and IGF-II). The encoded protein can be secreted into the bloodstream, where it binds IGF-I and IGF-II with high affinity, or it can remain intracellular, interacting with many different ligands. High expression levels of this protein promote the growth of several types of tumors and may be predictive of the chances of recovery of the patient. Several transcript variants, one encoding a secreted isoform and the others encoding nonsecreted isoforms, have been found for this gene. The IGFBP2 protein is consisted of 325 amino acids and its molecular mass is approximately 34.8 kDa.

What is the function of IGFBP2 protein?

IGFBP2 can bind to insulin-like growth factor (IGF) to regulate the activity of IGF thus reducing the effect of IGF on cell proliferation and differentiation. Their interaction can activate caspase enzyme family and induce cell apoptosis; also it can activate MAPK signaling pathway, thus promoting cell movement and migration. In addition, it can activate the PI3K/Akt signaling pathway, thus promoting cell proliferation and differentiation.

IGFBP2 related Signaling pathways

The signaling pathways of IGFBP2 can be divided into IGFS-dependent and IGFS-independent. In the IGFS-dependent form, IGF binds to IGF1R to activate the intracellular IGF signaling pathway. In IGFS-independent forms, IGFBP2 interacts with ligands other than IGFs to regulate transcription, induces apoptosis and repairs DNA damage. For example, IGFBP2 acts synergistically with β-catenin signaling pathway to regulate the occurrence and development of tumors. Or participates in MAPK/ERK signaling pathway and PI3K/AKT/mTOR signaling pathway.

IGFBP2 Related Diseases

IGFBP2 inhibits the effects of IGF on cell proliferation and differentiation, so IGFBP2 expression is often reduced in cancer. Dysfunctional IGFBP2 also affects insulin regulation and the proliferation, differentiation or migration of some important cells, leading to diabetes, cardiovascular disease and obesity.

Fig1. High baseline tumor burden-associated macrophages promote an immunosuppressive microenvironment and reduce the efficacy of immune checkpoint inhibitors through the IGFBP2-STAT3-PD-L1 pathway.

Bioapplications of IGFBP2

IGFBP2 is a protein that has diverse bioapplications, ranging from cancer to growth and development, diabetes, neurological disorders, and metabolic disorders. Further research is needed to fully understand its mechanisms of action and exploit its therapeutic potential, understanding the involvement of IGFBP2 in these diseases can contribute to the development of novel diagnostic and therapeutic strategies.