The RFG oligomerization domain mediates kinase activation and re-localization of the RET/PTC3 oncoprotein to the plasma membrane

Oncogene
C MonacoMassimo Santoro

Abstract

The RET/PTC3 oncogene arises from the fusion between the N-terminal encoding domain of the RFG gene and the tyrosine kinase encoding domain of RET receptor. RET/PTC3 is very frequent in papillary thyroid carcinomas, especially in children exposed to the Chernobyl accident. We have studied the functional consequences of the RFG-RET fusion. Here we show that the N-terminal coiled-coil domain of RGF mediates oligomerization and activation of the kinase and of the transforming capability of RET/PTC3. In addition, the RFG coiled-coil domain mediates a physical association between RET/PTC3 and RGF proteins, rendering RFG a bona fide substrate of RET/PTC3 kinase. Finally, we show that the coiled-coil domain of RGF is essential for the distribution of the RET/PTC3 protein at the membrane/particulate cell compartment level, where also most of the RFG protein is localized. We propose that fusion to the RFG coiled-coil domain provides RET kinase with a scaffold that mediates oligomerization and re-localization of the RET/PTC3 protein, a process that may be crucial for the signalling of this specific RET/PTC variant.

References

Sep 1, 1993·Molecular and Cellular Biology·F FazioliP P Di Fiore
Feb 1, 1994·Current Opinion in Genetics & Development·G A Rodrigues, M Park
May 28, 1996·Proceedings of the National Academy of Sciences of the United States of America·S Yeh, C Chang
May 31, 1996·The Journal of Biological Chemistry·K DurickS S Taylor
Apr 4, 1997·The Journal of Biological Chemistry·Q TongS M Jhiang
Oct 23, 1997·Proceedings of the National Academy of Sciences of the United States of America·L J HuangS S Taylor
Feb 12, 1998·Science·T Pawson, J D Scott
Apr 7, 1998·Molecular and Cellular Biology·K DurickS S Taylor
Jun 17, 1998·Molecular Endocrinology·E TreuterJ A Gustafsson
Nov 14, 1998·The Journal of Clinical Endocrinology and Metabolism·S L SuggS L Asa
Feb 23, 1999·Recent Results in Cancer Research. Fortschritte Der Krebsforschung. Progrès Dans Les Recherches Sur Le Cancer·M A PierottiI Bongarzone
Jun 5, 1999·Molecular and Cellular Neurosciences·M S AiraksinenM Saarma
Mar 22, 2001·Molecular and Cellular Biology·R M MelilloA Fusco

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Citations

Oct 18, 2013·Nature Reviews. Cancer·Alice T ShawJeffrey A Engelman
Nov 15, 2001·Advances in Anatomic Pathology·G Tallini, S L Asa
Dec 27, 2011·Endocrine-related Cancer·Dario PalmieriMonica Fedele
Feb 16, 2016·Journal of Molecular Biology·Gabriele Zaffagnini, Sascha Martens
May 27, 2008·Endocrinology and Metabolism Clinics of North America·Maria Domenica Castellone, Massimo Santoro
Mar 26, 2003·Journal of Cellular Physiology·Luisella AlbertiMarco A Pierotti
Sep 21, 2007·Proteomics·Giovanna Maria PierantoniAlfredo Fusco
Jun 10, 2014·Molecular Cell·Roberto BellelliFrancesca Carlomagno
Jul 3, 2002·Nature Reviews. Cancer·Dillwyn Williams
Feb 27, 2016·Biomarkers in Cancer·Bhavna S ParatalaKim M Hirshfield
Apr 17, 2003·British Journal of Cancer·N KonishiS Noguchi
Jan 16, 2003·Oncogene·Maria Domenica CastelloneMassimo Santoro
Nov 15, 2017·Nature Reviews. Clinical Oncology·Alexander DrilonDaniel S W Tan
Apr 2, 2019·Frontiers in Neuroscience·Maria Quiles Del Rey, Joseph D Mancias
Nov 18, 2018·Nature Communications·Bhavna S ParatalaKim M Hirshfield
Jul 18, 2014·International Journal of Food Sciences and Nutrition·Marco SarnoMerlin Nanayakkara
Oct 27, 2018·Pharmaceuticals·Naiara Santana-Codina, Joseph D Mancias
Apr 25, 2020·Genes·Massimo SantoroFrancesca Carlomagno
Apr 11, 2019·International Journal of Food Sciences and Nutrition·Marianna GalloRoberto Nigro
Mar 18, 2021·The FEBS Journal·Andrea Gubas, Ivan Dikic
Feb 14, 2007·Journal of Chemical Information and Modeling·Tiziano TuccinardiMaurizio Botta

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