Differential interaction of Enigma protein with the two RET isoforms |
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Authors: | Borrello Maria Grazia Mercalli Elena Perego Carla Degl'Innocenti Debora Ghizzoni Simona Arighi Elena Eroini Barbara Rizzetti Maria Grazia Pierotti Marco A |
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Affiliation: | Department of Experimental Oncology, Research Unit #3, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy. mariagrazia.borrello@istitutotumori.mi.it |
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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. |
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Keywords: | Enigma RET RET isoforms Tyrosine kinase Oncoproteins |
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