Differential interaction of Enigma protein with the two RET isoforms

Biochem Biophys Res Commun. 2002 Aug 23;296(3):515-22. doi: 10.1016/s0006-291x(02)00886-0.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / analysis
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cytoskeletal Proteins
  • Drosophila Proteins*
  • Intracellular Signaling Peptides and Proteins*
  • LIM Domain Proteins
  • Mice
  • Molecular Sequence Data
  • Precipitin Tests
  • Protein Isoforms / analysis
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases / analysis
  • Receptor Protein-Tyrosine Kinases / chemistry
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Sequence Alignment

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cytoskeletal Proteins
  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins
  • PDLIM7 protein, human
  • Pdlim7 protein, mouse
  • Protein Isoforms
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases
  • Ret protein, Drosophila
  • Ret protein, mouse