Disease relevance of IGF1R

• Antiproliferative and apoptotic effect of ascorbyl stearate in human glioblastoma multiforme cells: modulation of insulin-like growth factor-I receptor (IGF-IR) expression [1].
• Effects of estriol on proliferative activity and expression of insulin-like growth factor-I (IGF-I) and IGF-I receptor mRNA in cultured human osteoblast-like osteosarcoma cells [2].
• The paper comprehensively characterizes a decrease in the glycosylation of the insulin receptor in scrapie-infected neuroblastoma cells, but no change in glycosylation of the insulin-like growth factor-1 receptor [3].
• Plasma IGF-I concentrations and IGF-I receptor binding on mononuclear cells have been studied on bovine leukemia virus (BLV)-negative (CO), BLV-infected aleukemic (AL) cows or cows with persistent lymphocytosis (PL) [4].

High impact information on IGF1R

• When quiescent cultures of bovine fibroblasts were stimulated with 10 nM IGF-I and total cell lysates immunoblotted with anti-phosphotyrosine antibody, we observed a band at approximately 97 kDa, representing the beta-subunit of the IGF-I receptor, and a predominant tyrosyl-phosphorylated species migrating as a broad band between 170 and 190 kDa [5].
• These studies suggest that insulin, via interaction with insulin receptors on bovine fibroblasts, regulates IGF-I action at a step distal to IGF-I receptor binding and are consistent with desensitization occurring at an intracellular step in the mitogenic pathway shared by insulin and IGF-I [6].
• In the present study, we use this model system to determine insulin and IGF-I receptor interplay in the regulation of proto-oncogenes involved in mitogenesis [7].
• These findings demonstrate a cascade of insulin and IGF-I receptor tyrosine kinase-mediated pathways in the bovine luteal cell, manifested as increased activity of signal transduction enzymes and increased DNA synthesis [8].
• The potential role of insulin and IGF-I receptor tyrosine kinases in the bovine luteal cell was investigated in terms of autophosphorylation of the receptor and phosphorylation of endogenous and exogenous substrates [8].

Biological context of IGF1R

• These findings suggest that the stimulation of embryonic development by insulin and IGF-I is mediated through the IGF-I receptor [9].
• The number of insulin-like growth factor-I receptors far exceeds the number of insulin receptors in bovine corneal endothelium, suggesting that the effects of insulin on c-fos gene expression and mitogenesis were likely to be mediated through the insulin-like growth factor-I receptor [10].
• The inhibition of IGF-1-mediated cell proliferation was accompanied by abrogation of IGF-1 receptor tyrosine autophosphorylation [11].
• Iodine-125-labeled IGF-I ([125I]IGF-I) binding was characteristic of the IGF-I receptor, and binding kinetics as well as receptor densities were similar in cortical and medullary membranes [12].
• Competitive binding revealed that half-maximal inhibition of 125I-labelled IGF-I binding by IGF-I was approximately 3 micrograms/l. Dissociation rate constant of the IGF-I receptor was 3.10 +/- 0.06 nmol/l (S.E.M.) with a receptor site concentration of 366 +/- 8 fmol/mg protein for the average of three experiments [13].

Anatomical context of IGF1R

• Preincubation of bovine fibroblasts with concentrations of insulin that did not bind to the IGF-I receptor resulted in complete but reversible cellular desensitization to IGF-I-stimulated mitogenesis [6].
• Insulin-like growth factor-1 receptor in the cultured cells was also demonstrated immunohistochemically [14].
• The tyrosine kinase activity of the IGF-I receptor presumably mediates the effects of IGF-I on chromaffin cell function [15].
• The expressions of insulin-like growth factor-1 mRNA and insulin-like growth factor-1 receptor in disc tissue were greater in cells of the nucleus pulposus of fetal bovine intervertebral discs than in those of the adult discs [14].
• In both regions of the bovine adrenal gland the IGF-II/M6P receptor is much more abundant than the IGF-I receptor [12].

Associations of IGF1R with chemical compounds

• Data from crosslinking experiments with and without neuraminidase treatment indicate that the binding subunits of the retinal IGF-I receptor exist in two subpopulations (Mr = 121- and 131 kDa), and that the larger of the two subunits has either a greater number or more exposed sialic acid residues [16].
• IGF-I significantly increased thymidine incorporation, and its effect was completely inhibited by IGF-I receptor antibody [17].
• Taken together, our results indicate not only the presence of both IGF-I and IGF-II/Man6P receptors on BAM, but also provide evidence of the linkage of the IGF-I receptor to the inositol phosphate system [18].

Regulatory relationships of IGF1R

• IGF-I and IGF-II stimulated tyrosine kinase activity and autophosphorylation of the IGF-I receptor beta-subunit (Mr approximately 94,000) with equal potency (ED50 approximately 1 nM), whereas insulin was approximately 5 times less potent [19].

Other interactions of IGF1R

• Transcripts of the IGF-1 receptor (r) and IGF binding protein (BP)-2 were detected in all embryos, regardless of origin [20].

Analytical, diagnostic and therapeutic context of IGF1R

• This phosphoprotein was further identified as the autophosphorylated beta-subunit of the insulin/IGF-I receptor by immunoprecipitation with an anti-beta-subunit receptor antibody [8].
• However, JB1 significantly increased the number of TUNEL positive cells in the subependymal zone, suggesting that IGF-1 receptor is involved in the survival of subependymal neurons [21].
• Linkage mapping of the bovine insulin-like growth factor-1 receptor gene [22].

References