The insulin-like growth factor-binding protein (IGFBP) family and its role in obesity and cancer
Journal Title: Biomedical Journal of Scientific & Technical Research (BJSTR) - Year 2019, Vol 13, Issue 4
Abstract
Insulin-like growth factors (IGFs) plays an interesting role as a growth factor. Its function is mainly modulated by family of IGF binding proteins (IGFBPs). There are six important members, which maintain a structural and functional similarity and perform different functions. Several studies have linked IGFBPs to obesity, insulin resistance, metabolic syndrome and cancer. In this article, we provide the most relevant and recent implication of IGFBPs member in obesity and cancer, and some approach of each member as a therapeutic target or biological biomarker.Insulin-like growth factors (IGFs) are a protein family that actively participate in mammalian development and growth [1]. These hormones function as the main mediator of somatic growth mediated by growth hormone (GH), as well as an important component of GH-independent anabolic responses [2,3]. The mechanism of action of IGF need a complex system to act, often, it is known as the IGF “axis” system. This system should include two IGFs type as IGF-type 1 (IGF-1) and IGF-type 2 (IGF-2), two cell-surface receptors such as IGF-receptor type 1 (IGF-1R) and IGF-receptor type 2 (IGF-2R), specific to each IGFs type with tyrosine kinase activity and a family of IGF binding proteins (IGFBPs) [4]. The response of the IGF/IGF-receptor binding results in kinase activation and initiation of intracellular signaling via the serine/threonine-protein kinase (AKT) pathway (Figure 1) [5]. Interestingly, the IGFBPs family modulate the signaling process since it regulates the biological actions of IGFs in two different ways, the IGF receptor-dependent model (IGFBPs can act as an inhibitor, preventing the IGF/IGF-receptor association and as an activator, facilitating binding with IGF receptors) and IGF receptor-independent model (increasing the half-lives of the IGFs or providing a means of functional and/or tissue specificity) [6]. There are a six well characterized high affinity mammalian IGFBPs genes, designated IGFBP-1 through -6, and another not well-defined low affinity IGFBPs family, since IGFBP-7 to -10. Together, they constitute the IGFBP superfamily [7]. The primary structures of high-affinity binding IGFBPs family contain three principal domains: The N-terminal domain, the mid-region and the C-terminal domain. The N-terminal domain share approximately 58% of sequence between the six component of the high-affinity IGFBPs. This domain is characterized by containing 12 cysteine residues highly conserved. Within this domain, a local motif (GCGCCxxC) is also well conserved among the IGFBPs. However, the significance of this motif is as yet unknown [7-9]. The mid-region separates the N- from the C-terminal domain. The sequence for this domain appears to be unique to the family members. Two principal post-transductional modifications are present into. There are glycosylation and phosphorylation. The ability to bind to IGFs with high affinity appears not be influenced by N- or O-glycosylation, although there may be effects on resistance to proteolysis.
Authors and Affiliations
Hatim Boughanem, Amanda Cabrera Mulero, Manuel Macias Gonzalez M
Keywords
Related Articles
- EP ID EP585801
- DOI 10.26717/BJSTR.2019.13.002436
- Views 145
- Downloads 0
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