Role of the TFG N-terminus and coiled-coil domain in the transforming activity of the thyroid TRK-T3 oncogene

Angela Greco, Lisa Fusetti, Claudia Miranda, Riccardo Villa, Simona Zanotti, Sonia Pagliardini, Marco A. Pierotti

Research output: Contribution to journalArticle

Abstract

The thyroid TRK-T3 oncogene results from the fusion of the tyrosine kinase (TK) domain of NTRK1 (one of the receptors for the Nerve Growth Factor) on chromosome 1 to sequences of a novel gene, TFG, on chromosome 3. The 68 kDa TRK-T3 fusion oncoprotein displays a constitutive tyrosine kinase activity resulting in its capability to transform mouse NIH3T3 cells. The TFG portion of TRK-T3 contains a coiled-coil domain most likely responsible for the constitutive, ligand-independent activation of the receptor tyrosine kinase activity. We have previously shown that TRK-T3 oncoprotein forms, in vivo, complexes of three or four molecules. By mean of different experimental approaches, we show here that TRK-T3 activity depends on oligomers formation. In addition, the analysis of different TRK-T3 mutants indicates that the TFG coiled-coil domain and its N-terminal region are both required for the activation and the fully transforming activity of the TRK-T3 oncoprotein, although, most likely, they play a role in different steps of the transforming process. The deletion of the coiled-coil domain abrogates the oligomers formation leading to a constitutive activation; the deletion of the N-terminal region, although not affecting phosphorylation and complexes formation, abrogates transformation, thus suggesting a role in cellular localization and/or interaction with substrata.

Original languageEnglish
Pages (from-to)809-816
Number of pages8
JournalOncogene
Volume16
Issue number6
Publication statusPublished - Feb 12 1998

Keywords

  • Coiled-coil domain
  • Oncogenic transformation
  • TRK oncogenes

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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  • Cite this

    Greco, A., Fusetti, L., Miranda, C., Villa, R., Zanotti, S., Pagliardini, S., & Pierotti, M. A. (1998). Role of the TFG N-terminus and coiled-coil domain in the transforming activity of the thyroid TRK-T3 oncogene. Oncogene, 16(6), 809-816.