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Protein Stability of Wild Type and Mutant forms of the RET Tyrosine Kinase
Author(s) -
Vega Quinn,
Maslovski Shani
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.758.17
Subject(s) - mutant , receptor tyrosine kinase , biology , signal transduction , tyrosine kinase , receptor , mutation , gene , wild type , transfection , protein kinase a , microbiology and biotechnology , kinase , cancer research , genetics
The ret proto‐oncogene encodes a trans‐membrane receptor tyrosine kinase that plays a key role in neural differentiation as well as development of the enteric nervous system and kidneys. Mutations of the RET gene have been associated with several cancers such as MEN2A, MEN2B and FMTC; however, the down‐regulation mechanism is largely unknown, especially between these various forms of RET. In order to analyze the effect of the mutated form of RET on signal transduction and down‐regulation, VERO cells were transfected with wild type and activated forms of RET and the effect of RET mutations on protein degradation analyzed. The degradation studies show that MEN2B has a lower level of protein expression and protein degradation, compared to wild type RET. The decrease in RET protein levels inversely correlates with levels of the ubiquitin pathway enzyme, Cbl. The connection between decreased MEN2B down regulation and the loss of Cbl provides a possible explanation for the mutant receptor's oncogenic potential.