Insulin-Like Growth Factors (IGF), Fragments & Related Peptides

Introduction

The insulin-like growth factors (IGF) is a group of polypeptides with growth-promoting effects. The secretory cells are widely distributed in tissues such as liver, kidney, lung, heart, brain and intestine. The IGFs family consists of two low molecular peptides (IGF-I, IGF-II), two types of specific receptors including IGF-IR and IGF-IIR, and six binding proteins (IGF binding proteins, IGFBP), in which the IGF-I, IGF-II play an active role in cell proliferation and exist in association with distinct and specific IGF-binding proteins designated as IGFBPs 1–6 and possibly IGFBP-related proteins (IGFBP-rPs). The IGF must bind to the carrier protein IGF binding protein (IGFBP) to bind to its specific receptor to exert biological effects. The structure of IGF-IR is different with the IGF-IIR, and the former structure is similar to the insulin receptor (Ir), and is composed of two subunits of α and β, and a glycoprotein of α2β2 tetramer, in which the α subunit is the ligand binding site and theβ subunit has intrinsic tyrosine kinase activity without tyrosinase activity.

Mechanism of action

Unlike other growth factors, the biological activity of the IGFs within tissues and the circulation is modified by six IGFBPs. These proteins have individual and specific expression patterns and exert different functions including stimulation or inhibition of IGF bioactivity as well as IGF-independent actions. IGF exerts its biological effects by target cell surface receptors IGF-IR and IGF-IIR through endocrine, paracrine and/or autocrine methods and is regulated by IGF binding proteins. Most extrahepatic tissues can produce IGF locally, and most of them are not regulated by growth hormone (GH), and play an important role in local tissues.

Application of IGF

Owing to the features of IGF, which can be applied in the diseases such as osteoporosis, diabetes (especially type II), and angiocardiopathy. Furthermore, in recent years, a large number of studies have shown that the level of IGFs in the blood is increased, which is positively correlated with the incidence of malignant tumors such as breast cancer, lung cancer, liver cancer, gastric cancer and colon cancer. The study of signaling pathway of IGFs is expected to provide strong help in the fields including early diagnosis of tumor and molecular targeted therapy.

References

1. Devi G. R., Yang D. H., Rosenfeld R. G., & Oh Y. (2000). Differential effects of insulin-like growth factor (IGF)-binding protein-3 and its proteolytic fragments on ligand binding, cell surface association, and IGF-I receptor signaling. Endocrinology, 141(11), 4171-4179.
2. Kiepe D., Van D. P. A., Ciarmatori S., Standker L., Schutt B., Hoeflich A., Hugel U., Oh J., & Tonshoff B. (2008). Defined carboxy-terminal fragments of insulin-like growth factor (IGF) binding protein-2 exert similar mitogenic activity on cultured rat growth plate chondrocytes as IGF-I. Endocrinology, 149(10), 4901-4911.
3. Mark S., Kubler B., Honing S., Oesterreicher S., John H., Braulke T., Forssmann W. G., Standker L. (2005). Diversity of Human Insulin-like Growth Factor (IGF) Binding Protein-2 Fragments in Plasma: Primary Structure, IGF-Binding Properties, and Disulfide Bonding Pattern. Biochemistry, 44(9), 3644-3652.