The insulin-like growth factor binding proteins (IGFBPs), as high affinity IGF binding partners, are the principal regulators of IGF-1 and IGF-2 action. Accordingly, effects of IGFBPs can be observed on the levels of growth and differentiation, development, metabolism, and lifespan. The diversity of IGFBP-actions arises due to time-, sex-, and tissue-specific expression of the six distinct IGFBPs (IGFBP-1 to−6), which have redundant functions as seen from the analysis of double-, triple-, or quadruple IGFBP-knockout mice. The complexity of IGFBP functions is related not only to their roles as IGF carriers within the circulation but also to actions within the extracellular space and in distinct subcellular compartments, such as the cell nucleus. IGFBP functions have been attributed to structural motifs in the three conserved IGFBP subdomains, with specific residues being posttranslationally modified by glycosylation or phosphorylation to regulate IGFBP action. In addition, multiple binding partners inside and outside the cell have been identified that regulate IGFBP functions, including their IGF-independent activities. Furthermore, an in-depth understanding is emerging of the role of IGFBP proteolysis in the regulation of both IGF-dependent and IGF-independent actions through generation of potentially bioactive IGFBP-fragments. Accordingly, proteolytic degradation of IGFBPs as a physiologically relevant mechanism in disease has been revealed both in a malignant context but also in other acute or chronic pathophysiological conditions. Finally, the IGFBPs e.g., as sensors of GH/IGF-status have tremendous biomarker potential. Measurement of IGFBP-3/IGFBP-2 ratios provides ultimate sensitivity for the GH-status of a given cellular system. Similarly, detection of intact and fragmented IGFBPs may provide an indication of disease status. Accordingly, for the future we may expect an evolution of IGFBP-related diagnostic approaches, which extend to the characterization of both structural and functional properties of IGFBPs and their fragments in preclinical and clinical research.
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- Insulin-like growth factor-binding proteins
- biomarker research
- farm animals