Constitutive activation of the RON gene promotes invasive growth but not transformation

Massimo M. Santoro, Chiara Collesi, Silvia Grisendi, Giovanni Gaudino, Paolo M. Comoglio

Research output: Contribution to journalArticle

Abstract

MET, RON, and SEA are members of a gene family encoding tyrosine kinase receptors with distinctive properties. Besides mediating growth, they control cell dissociation, motility ('scattering'), and formation of branching tubules. While there are transforming counterparts of MET and SEA, no oncogenic forms of RON have yet been identified. A chimeric Tpr-Ron, mimicking the oncogenic form of Met (Tpr-Met) was generated to investigate its transforming potential. For comparison, a chimeric Tpr-Sea was also constructed. Fusion with Tpr induced constitutive activation of the Ron and Sea kinases. While Tpr-Sea was more efficient than Tpr-Met in transformation, Tpr-Ron did not transform NIH 3T3 cells. The differences in the transforming abilities of Tpr-Met and Tpr-Ron were linked to the functional features of the respective tyrosine kinases using the approach of swapping subdomains. Kinetic analysis showed that the catalytic efficiency of Tpr-Ron is five times lower than that of Tpr-Met. Moreover, constitutive activation of Ron resulted in activation of the MAP kinase signaling cascade approximately three times lower than that attained by Tpr-Met. However, constitutive activation of Ron did induce a mitogenic-invasive response, causing cell dissociation, motility, and invasion of extracellular matrices. Tpr-Ron also induced formation of long, unbranched tubules in tridimensional collagen gels. These data show that RON has the potential to elicit a motile-invasive rather than a transformed phenotype.

Original languageEnglish
Pages (from-to)7072-7083
Number of pages12
JournalMolecular and Cellular Biology
Volume16
Issue number12
Publication statusPublished - 1996

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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  • Cite this

    Santoro, M. M., Collesi, C., Grisendi, S., Gaudino, G., & Comoglio, P. M. (1996). Constitutive activation of the RON gene promotes invasive growth but not transformation. Molecular and Cellular Biology, 16(12), 7072-7083.