Differential interaction of Enigma protein with the two RET isoforms.
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.
Mesh Terms:
3T3 Cells, Amino Acid Sequence, Animals, Carrier Proteins, Cell Line, Drosophila Proteins, Intracellular Signaling Peptides and Proteins, Mice, Molecular Sequence Data, Precipitin Tests, Protein Isoforms, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-ret, Receptor Protein-Tyrosine Kinases, Sequence Alignment
3T3 Cells, Amino Acid Sequence, Animals, Carrier Proteins, Cell Line, Drosophila Proteins, Intracellular Signaling Peptides and Proteins, Mice, Molecular Sequence Data, Precipitin Tests, Protein Isoforms, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-ret, Receptor Protein-Tyrosine Kinases, Sequence Alignment
Biochem. Biophys. Res. Commun.
Date: Aug. 23, 2002
PubMed ID: 12176011
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