Characterization of IRA/IRB hybrid insulin receptors using bioluminescence resonance energy transfer

Biochemical Pharmacology
Christophe BlanquartT Issad

Abstract

The insulin receptor (IR) is composed of two alpha-chains that bind ligands and two beta-chains that possess an intracellular tyrosine kinase activity. The IR is expressed in cells as two isoforms containing or not exon 11 (IRB and IRA, respectively). Several mRNA studies have demonstrated that the two isoforms are co-expressed in different tissues and in several cancer cells. IRA/IRB hybrid receptors, constituting of an alphabeta-chain from IRA and an alphabeta-chain from IRB, are likely to occur in cells co-expressing both isoforms, but their study has been hampered by the lack of specific tools. In previous work, we used BRET to study IR and IGF1R homodimers and heterodimers. Here, we have used BRET to characterize IRA/IRB hybrids. BRET saturation experiments showed that IRA/IRB hybrids are randomly formed in cells. Moreover, by co-transfecting HEK-293 cells with a luciferase-tagged kinase-dead version of one isoform and a wild-type untagged version of the other isoform, we showed that IRA/IRB hybrids can recruit, upon ligand stimulation, a YFP-tagged intracellular partner. Finally, using BRET, we have studied ligand-induced conformational changes within IRA/IRB hybrids. Dose-response experiments showed that hybrid receptors...Continue Reading

References

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Citations

Nov 20, 2008·Journal of Mammary Gland Biology and Neoplasia·Antonino Belfiore, Francesco Frasca
Aug 24, 2010·Acta Diabetologica·R VigneriL Sciacca
Dec 29, 2015·Archives of Physiology and Biochemistry·Patrick PagesyTarik Issad
Oct 20, 2010·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·Yangxin Li, Yong-Jian Geng
May 7, 2015·Biochemical and Biophysical Research Communications·Yann FardiniTarik Issad
May 1, 2012·Cellular and Molecular Bioengineering·Angelina E AltshulerGeert W Schmid-Schönbein
Oct 29, 2014·World Journal of Hepatology·Mónica Enguita-Germán, Puri Fortes
Feb 14, 2019·International Journal of Molecular Sciences·Angelo CignarelliFrancesco Giorgino
May 3, 2018·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Midori HonmaHideki Katagiri
Oct 3, 2015·Diabetes/metabolism Research and Reviews·F WestermeierL Sobrevia
Jun 6, 2019·Frontiers in Endocrinology·Gaelle FilhoulaudCatherine Postic
Nov 21, 2018·International Journal of Molecular Sciences·Veronica VellaLaura Sciacca
Sep 11, 2020·Nature Reviews. Cancer·Emily J Gallagher, Derek LeRoith
Sep 27, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hasanain Al-MukhTarik Issad
Aug 9, 2019·Biochimica Et Biophysica Acta. Molecular Cell Research·Veronica VellaAntonino Belfiore
Feb 10, 2011·Journal of Cell Science·Jimena GiudiceElizabeth A Jares-Erijman
Aug 8, 2021·International Journal of Molecular Sciences·Andrea Olmos-OrtizVerónica Zaga-Clavellina
Apr 4, 2009·Journal of Chromatography. a·T F H Bovee, M G Pikkemaat

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