Format

Send to

Choose Destination
J Mol Endocrinol. 2018 Jul;61(1):T11-T28. doi: 10.1530/JME-17-0254. Epub 2017 Dec 18.

IGF-binding proteins.

Author information

1
Department of Medicine (Alfred)Monash University, Melbourne, Australia leon.bach@monash.edu.
2
Department of Endocrinology and DiabetesAlfred Hospital, Melbourne, Australia.

Abstract

Insulin-like growth factor-binding proteins (IGFBPs) 1-6 bind IGFs but not insulin with high affinity. They were initially identified as serum carriers and passive inhibitors of IGF actions. However, subsequent studies showed that, although IGFBPs inhibit IGF actions in many circumstances, they may also potentiate these actions. IGFBPs are widely expressed in most tissues, and they are flexible endocrine and autocrine/paracrine regulators of IGF activity, which is essential for this important physiological system. More recently, individual IGFBPs have been shown to have IGF-independent actions. Mechanisms underlying these actions include (i) interaction with non-IGF proteins in compartments including the extracellular space and matrix, the cell surface and intracellular space, (ii) interaction with and modulation of other growth factor pathways including EGF, TGF-β and VEGF, and (iii) direct or indirect transcriptional effects following nuclear entry of IGFBPs. Through these IGF-dependent and IGF-independent actions, IGFBPs modulate essential cellular processes including proliferation, survival, migration, senescence, autophagy and angiogenesis. They have been implicated in a range of disorders including malignant, metabolic, neurological and immune diseases. A more complete understanding of their cellular roles may lead to the development of novel IGFBP-based therapeutic opportunities.

KEYWORDS:

binding protein; cellular actions; insulin-like growth factor; protein structure; regulation

PMID:
29255001
DOI:
10.1530/JME-17-0254

Supplemental Content

Full text links

Icon for Sheridan PubFactory
Loading ...
Support Center