Oncogenic RET Receptors Display Different Autophosphorylation Sites and Substrate Binding Specificities

Authors

Xin Liu, University of Michigan, Ann Arbor
Quinn Vega, Montclair State UniversityFollow
Ruth A. Decker, University of Michigan, Ann Arbor
Akhilesh Pandey, University of Michigan, Ann Arbor
Carolyn A. Worby, University of Michigan, Ann Arbor
Jack E. Dixon, University of Michigan, Ann Arbor

Document Type

Article

Publication Date

3-8-1996

Journal / Book Title

Journal of Biological Chemistry

Abstract

The c-ret proto-oncogene encodes a receptor tyrosine kinase which plays an important role in neural crest as well as kidney development. Genetic studies have demonstrated that germ line mutations in the ret oncogene are the direct cause of multiple endocrine neoplasia (MEN) 2A and 2B, familial medullary thyroid carcinoma (FMTC), and Hirschsprung's disease. However, despite the large body of genetic and biological evidence suggesting the importance of RET in development and neoplastic processes, the signal transduction mechanisms of RET remain unknown. To begin to understand the molecular mechanisms of the disease states caused by mutations in RET, the patterns of autophosphorylation of the wild-type RET and the MEN mutants were studied using site-directed mutagenesis and phosphopeptide mapping. Among the 6 autophosphorylation sites found in the wild-type RET receptor, the MEN2B mutant lacked phosphorylation at Tyr-1096, leading to decreased Grb2 binding, while simultaneously creating a new phosphorylation site. These changes in autophosphorylation suggest that the MEN2B mutation may result in the more aggressive MEN2B phenotype by altering the receptor's signaling capabilities.

Comments

This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

DOI

10.1074/jbc.271.10.5309

MSU Digital Commons Citation

Liu, Xin; Vega, Quinn; Decker, Ruth A.; Pandey, Akhilesh; Worby, Carolyn A.; and Dixon, Jack E., "Oncogenic RET Receptors Display Different Autophosphorylation Sites and Substrate Binding Specificities" (1996). Department of Mathematics Facuty Scholarship and Creative Works. 128.
https://digitalcommons.montclair.edu/mathsci-facpubs/128

Published Citation

Liu, X., Vega, Q. C., Decker, R. A., Pandey, A., Worby, C. A., & Dixon, J. E. (1996). Oncogenic RET Receptors Display Different Autophosphorylation Sites and Substrate Binding Specificities (∗). Journal of Biological Chemistry, 271(10), 5309-5312.