scholarly journals Development of a Quantitative PCR Assay for Detection of Human Insulin-Like Growth Factor Receptor and Insulin Receptor Isoforms

Endocrinology ◽  
2016 ◽  
Vol 157 (4) ◽  
pp. 1702-1708 ◽  
Author(s):  
Clare A. Flannery ◽  
Anne M. Rowzee ◽  
Gina H. Choe ◽  
Farrah L. Saleh ◽  
Caitlin C. Radford ◽  
...  
Keyword(s):  
Growth Factor ◽  
Insulin Receptor ◽  
Splice Variants ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
Receptor Expression ◽  
Molecular Signature ◽  
Insulin Like Growth Factor ◽  
Insulin Receptor Isoforms ◽  
Signaling Receptors

Abstract The biological activity of insulin and the insulin-like growth factor (IGF) ligands, IGF-I and IGF-II, is based in part on the relative abundance and distribution of their target receptors: the insulin receptor (IR) splice variants A (IR-A) and B (IR-B) and IGF 1 receptor (IGF-1R). However, the relative quantity of all three receptors in human tissues has never been measured together on the same scale. Due to the high homology between insulin receptor (IR)-A and IR-B proteins and lack of antibodies that discern the two IR splice variants, their mRNA sequence is the most reliable means of distinguishing between the receptors. Hence, highly specific primers for IR-A, IR-B, and IGF-1R mRNA were designed to accurately detect all three receptors by quantitative RT-PCR and enable direct quantification of relative receptor expression levels. A standard concentration curve of cDNA from each receptor was performed. Assay specificity was tested using competition assays and postamplification analysis by gel electrophoresis and cloning. Forward and reverse primer concentrations were optimized to ensure equal efficiencies across primer pairs. This assay enables a specific molecular signature of IGF/insulin signaling receptors to be assayed in different tissues, cell types, or cancers.

scholarly journals Insulin Receptor Isoforms and Insulin Receptor/Insulin-Like Growth Factor Receptor Hybrids in Physiology and Disease

2009 ◽  
Vol 30 (6) ◽  
pp. 586-623 ◽  
Author(s):  
Antonino Belfiore ◽  
Francesco Frasca ◽  
Giuseppe Pandini ◽  
Laura Sciacca ◽  
Riccardo Vigneri
Keyword(s):  
Growth Factor ◽  
Insulin Receptor ◽  
Growth Factor Receptor ◽  
Insulin Like Growth Factor ◽  
Receptor Isoforms ◽  
Insulin Receptor Isoforms

scholarly journals Secretion of Annexin II via Activation of Insulin Receptor and Insulin-like Growth Factor Receptor

2002 ◽  
Vol 278 (6) ◽  
pp. 4205-4215 ◽  
Author(s):  
Wei-Qin Zhao ◽  
Gina H. Chen ◽  
Hui Chen ◽  
Alessia Pascale ◽  
Lakshmi Ravindranath ◽  
...  
Keyword(s):  
Growth Factor ◽  
Insulin Receptor ◽  
Growth Factor Receptor ◽  
Annexin Ii ◽  
Insulin Like Growth Factor

scholarly journals Determination of Alkali-Sensing Parts of the Insulin Receptor-Related Receptor Using the Bioinformatic Approach

Acta Naturae ◽  
2015 ◽  
Vol 7 (2) ◽  
pp. 80-86 ◽  
Author(s):  
I. E. Deyev ◽  
N. V. Popova ◽  
A. G. Petrenko
Keyword(s):  
Growth Factor ◽  
Insulin Receptor ◽  
Growth Factor Receptor ◽  
Ph Sensitive ◽  
Effective Concentration ◽  
The Body ◽  
Insulin Like Growth Factor ◽  
Extracellular Region ◽  
Half Maximal Effective Concentration ◽  
Receptor Family

IRR (insulin receptor-related receptor) is a receptor tyrosine kinase belonging to the insulin receptor family, which also includes insulin receptor and IGF-IR receptor. We have previously shown that IRR is activated by extracellular fluid with pH 7.9 and regulates excess alkali excretion in the body. We performed a bioinformatic analysis of the pH-sensitive potential of all three members of the insulin receptor family of various animal species (from frog to man) and their chimeras with swapping of different domains in the extracellular region. An analysis using the AcalPred program showed that insulin receptor family proteins are divided into two classes: one class with the optimal working pH in the acidic medium (virtually all insulin receptor and insulin-like growth factor receptor orthologs, except for the IGF-IR ortholog from Xenopus laevis) and the second class with the optimal working pH in the alkaline medium (all IRR orthologs). The program had predicted that the most noticeable effect on the pH-sensitive property of IRR would be caused by the replacement of the L1 and C domains in its extracellular region, as well as the replacement of the second and third fibronectin repeats. It had also been assumed that replacement of the L2 domain would have the least significant effect on the alkaline sensitivity of IRR. To test the in silico predictions, we obtained three constructs with swapping of the L1C domains, the third L2 domain, and all three domains L1CL2 of IRR with similar domains of the insulin-like growth factor receptor. We found that replacement of the L1C and L1CL2 domains reduces the receptors ability to be activated with alkaline pH, thus increasing the half-maximal effective concentration by about 100%. Replacement of the L2 domain increased the half-maximal effective concentration by 40%. Thus, our results indicate the high predictive potential of the AcalPred algorithm, not only for the pH-sensitive enzymes, but also for pH-sensitive receptors.

Upregulation of the Insulin Receptor and Type I Insulin-Like Growth Factor Receptor Are Early Events in Hepatocarcinogenesis

2011 ◽  
Vol 39 (3) ◽  
pp. 524-543 ◽  
Author(s):  
Eiman Aleem ◽  
Dirk Nehrbass ◽  
Fritz Klimek ◽  
Doris Mayer ◽  
Peter Bannasch
Keyword(s):  
Growth Factor ◽  
Insulin Receptor ◽  
Growth Factor Receptor ◽  
Type I ◽  
Insulin Like Growth Factor

scholarly journals Suppression of Cardiac Autophagy by Hyperinsulinemia in Insulin Receptor-Deficient Hearts Is Mediated by Insulin-Like Growth Factor Receptor Signaling

2019 ◽  
Vol 31 (6) ◽  
pp. 444-457
Author(s):  
Karla Maria Pires ◽  
Natalia S. Torres ◽  
Marcio Buffolo ◽  
River Gunville ◽  
Christin Schaaf ◽  
...  
Keyword(s):  
Growth Factor ◽  
Insulin Receptor ◽  
Growth Factor Receptor ◽  
Insulin Like Growth Factor ◽  
Receptor Signaling ◽  
Growth Factor Receptor Signaling

scholarly journals Differential Activation of Insulin Receptor Substrates 1 and 2 by Insulin-Like Growth Factor-Activated Insulin Receptors

2007 ◽  
Vol 27 (10) ◽  
pp. 3569-3577 ◽  
Author(s):  
Adam Denley ◽  
Julie M. Carroll ◽  
Gemma V. Brierley ◽  
Leah Cosgrove ◽  
John Wallace ◽  
...  
Keyword(s):  
Growth Factor ◽  
Insulin Receptor ◽  
Splice Variants ◽  
Biological Effects ◽  
Insulin Receptors ◽  
Insulin Like Growth Factor ◽  
Extracellular Signal ◽  
Igf I ◽  
High Concentrations ◽  
Kinase Pathway

ABSTRACT The insulin-like growth factors (insulin-like growth factor I [IGF-I] and IGF-II) exert important effects on growth, development, and differentiation through the IGF-I receptor (IGF-IR) transmembrane tyrosine kinase. The insulin receptor (IR) is structurally related to the IGF-IR, and at high concentrations, the IGFs can also activate the IR, in spite of their generally low affinity for the latter. Two mechanisms that facilitate cross talk between the IGF ligands and the IR at physiological concentrations have been described. The first of these is the existence of an alternatively spliced IR variant that exhibits high affinity for IGF-II as well as for insulin. A second phenomenon is the ability of hybrid receptors comprised of IGF-IR and IR hemireceptors to bind IGFs, but not insulin. To date, however, direct activation of an IR holoreceptor by IGF-I at physiological levels has not been demonstrated. We have now found that IGF-I can function through both splice variants of the IR, in spite of low affinity, to specifically activate IRS-2 to levels similar to those seen with equivalent concentrations of insulin or IGF-II. The specific activation of IRS-2 by IGF-I through the IR does not result in activation of the extracellular signal-regulated kinase pathway but does induce delayed low-level activation of the phosphatidylinositol 3-kinase pathway and biological effects such as enhanced cell viability and protection from apoptosis. These findings suggest that IGF-I can function directly through the IR and that the observed effects of IGF-I on insulin sensitivity may be the result of direct facilitation of insulin action by IGF-I costimulation of the IR in insulin target tissues.

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