Differential interaction of Enigma protein with the two RET isoforms

Maria Grazia Borrello, Elena Mercalli, Carla Perego, Debora Degl'Innocenti, Simona Ghizzoni, Elena Arighi, Barbara Eroini, Maria Grazia Rizzetti, Marco A. Pierotti

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)515-522
Number of pages8
JournalBiochemical and Biophysical Research Communications
Issue number3
Publication statusPublished - 2002


  • Enigma
  • Oncoproteins
  • RET
  • RET isoforms
  • Tyrosine kinase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology


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