Abstract
The receptor tyrosine kinase RET, with a known role in embryonic development and in human pathologies, is alternatively spliced to yield at least two functional isoforms, which differ only in their carboxyl terminal. Enigma protein is a member of the PDZ-LIM family and is known to interact with the short isoform of RET/PTC2, a chimeric oncoprotein isolated from papillary thyroid carcinoma. Here, we show that Enigma also interacts in intact cells with the short isoform of RET-wt and of its pathologic mutants associated to MEN2 syndromes, RET-C634R and RET-M918T. In contrast, Enigma binds all the corresponding RET long isoforms very poorly and colocalizes with short but not long RET/PTC2 isoforms. The RET docking tyrosine for Enigma is the last but one before the divergence between the two isoforms and we demonstrated that short-isoform-specific amino acid residues +2 to +4 to this tyrosine are required for the interaction of RET/PTC2 with Enigma.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Adaptor Proteins, Signal Transducing
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Amino Acid Sequence
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Animals
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Carrier Proteins / analysis
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Carrier Proteins / metabolism*
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Cell Line
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Cytoskeletal Proteins
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Drosophila Proteins*
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Intracellular Signaling Peptides and Proteins*
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LIM Domain Proteins
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Mice
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Molecular Sequence Data
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Precipitin Tests
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Protein Isoforms / analysis
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Protein Isoforms / chemistry
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Protein Isoforms / metabolism
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Proto-Oncogene Proteins / analysis
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Proto-Oncogene Proteins / chemistry
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-ret
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Receptor Protein-Tyrosine Kinases / analysis
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Receptor Protein-Tyrosine Kinases / chemistry
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Receptor Protein-Tyrosine Kinases / metabolism*
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Sequence Alignment
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Cytoskeletal Proteins
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Drosophila Proteins
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Intracellular Signaling Peptides and Proteins
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LIM Domain Proteins
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PDLIM7 protein, human
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Pdlim7 protein, mouse
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Protein Isoforms
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-ret
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Receptor Protein-Tyrosine Kinases
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Ret protein, Drosophila
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Ret protein, mouse