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IGF-1 is one of the most potent natural activators of the Akt signaling pathway, a stimulator of cell growth and proliferation, and a potent inhibitor of programmed cell death. [ 22 ] [ 23 ] The IGF-1 receptor and insulin receptor are two closely related members of a transmembrane tetrameric tyrosine kinase receptor family.
The insulin-like growth factor 1 (IGF-1) receptor is a protein found on the surface of human cells. It is a transmembrane receptor that is activated by a hormone called insulin-like growth factor 1 and by a related hormone called IGF-2. It belongs to the large class of tyrosine kinase receptors. This receptor mediates the effects of IGF-1 ...
The IGF-1 receptor is the "physiological" receptor. IGF-1 binds to it at significantly higher affinity than it binds the insulin receptor. Like the insulin receptor, the IGF-1 receptor is a receptor tyrosine kinase—meaning the receptor signals by causing the addition of a phosphate molecule on particular tyrosines. The IGF-2 receptor only ...
Approximately 98% of IGF-1 is always bound to one of six binding proteins (IGF-BP). IGFBP-3, the most abundant protein, accounts for 80% of all IGF binding. IGF-1 binds to IGFBP-3 in a 1:1 molar ratio. IGF-BP also binds to IGF-1 inside the liver, allowing growth hormone to continuously act upon the liver to produce more IGF-1.
The insulin receptor (IR) is a transmembrane receptor that is activated by insulin, IGF-I, IGF-II and belongs to the large class of receptor tyrosine kinase. [5] Metabolically, the insulin receptor plays a key role in the regulation of glucose homeostasis; a functional process that under degenerate conditions may result in a range of clinical manifestations including diabetes and cancer.
Insulin/IGF-1-like signaling is well-conserved evolutionarily across animal phyla, from single celled organisms to mammals. [7] DAF-2 is the only member of the insulin receptor family in C. elegans but it corresponds, in form and function, to multiple pathways in humans.
Insulin receptor substrate 1 (IRS-1) is a signaling adapter protein that in humans is encoded by the IRS1 gene. [5] It is a 180 kDa protein with amino acid sequence of 1242 residues. [ 6 ] It contains a single pleckstrin homology (PH) domain at the N-terminus and a PTB domain ca. 40 residues downstream of this, followed by a poorly conserved C ...
GH also stimulates, through the JAK-STAT signaling pathway, [39] the production of insulin-like growth factor 1 (IGF-1, formerly known as somatomedin C), a hormone homologous to proinsulin. [40] The liver is a major target organ of GH for this process and is the principal site of IGF-1 production. IGF-1 has growth-stimulating effects on a wide ...