IL-15/IL-15Rα intracellular trafficking in haman melanoma cells and signal transduction through the IL-15Rα

Raffaele Pereno, Julien Giron-Michel, Alessia Gaggero, Eric Cazes, Raffaella Meazza, Monia Monetti, Eugenia Monaco, Zohar Mishal, Claude Jasmin, Francesco Indiveri, Silvano Ferrini, Bruno Azzarone

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Abstract

There are two IL-15 isoforms and eight isoforms for the IL-15Rα chain whose biological role is poorly understood. Here, we have analysed the intracellular trafficking of IL-15 and IL-15Rα and tried to shed some light on their function(s). In IL-15/GFP CHO transfectants both IL-15 isoforms show nuclear localization. Two melanoma cell lines (MELP and MELREO) spontaneously expressing the IL-15 isoforms, display different intracellular trafficking of the IL-15/IL-15Rα complex. In MELP cells only IL-151α is detected inside the nucleus, whereas IL-15 and IL-15Rα assemble at the cell surface and are internalized. Moreover, the transducing molecule TRAF2 co-immunoprecipitates with IL-15Rα and may be deflected to TNFRI using anti-IL-15 blocking mAbs and TNF-α. By contrast, MELREO cells display IL-15Rα and IL-15 nuclear localization hut only a partial co-localization of these molecules on the cell surface. In these cells, TRAF2 is strongly associated with IL-15Rα and cannot be deflected by any treatment. Since TRAF2 activates the transcription factor NF-κB, IL-15 through IL-15Rα, could have a role in the control of this pathway. Indeed, anti-IL-15 MaB inhibit the constitutive nuclear localization of NFκB and the phosphorylation of its inhibitor Iκ-Bα. Thus, IL-15Rα controls NF-κB activation, however differences in the intracellular trafficking of the IL-15 and/or IL-15Rα suggest a different biological role for this complex in MELP versus MELREO cells.

Original languageEnglish
Pages (from-to)5153-5162
Number of pages10
JournalOncogene
Volume19
Issue number45
Publication statusPublished - Oct 26 2000

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Interleukin-15
Melanoma
Signal Transduction
TNF Receptor-Associated Factor 2
Protein Isoforms
Transcription Factors

Keywords

  • IL-15
  • IL-15Rα
  • Melanoma progression
  • NF-κB
  • Secretion pattern

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Pereno, R., Giron-Michel, J., Gaggero, A., Cazes, E., Meazza, R., Monetti, M., ... Azzarone, B. (2000). IL-15/IL-15Rα intracellular trafficking in haman melanoma cells and signal transduction through the IL-15Rα. Oncogene, 19(45), 5153-5162.

IL-15/IL-15Rα intracellular trafficking in haman melanoma cells and signal transduction through the IL-15Rα. / Pereno, Raffaele; Giron-Michel, Julien; Gaggero, Alessia; Cazes, Eric; Meazza, Raffaella; Monetti, Monia; Monaco, Eugenia; Mishal, Zohar; Jasmin, Claude; Indiveri, Francesco; Ferrini, Silvano; Azzarone, Bruno.

In: Oncogene, Vol. 19, No. 45, 26.10.2000, p. 5153-5162.

Research output: Contribution to journalArticle

Pereno, R, Giron-Michel, J, Gaggero, A, Cazes, E, Meazza, R, Monetti, M, Monaco, E, Mishal, Z, Jasmin, C, Indiveri, F, Ferrini, S & Azzarone, B 2000, 'IL-15/IL-15Rα intracellular trafficking in haman melanoma cells and signal transduction through the IL-15Rα', Oncogene, vol. 19, no. 45, pp. 5153-5162.
Pereno R, Giron-Michel J, Gaggero A, Cazes E, Meazza R, Monetti M et al. IL-15/IL-15Rα intracellular trafficking in haman melanoma cells and signal transduction through the IL-15Rα. Oncogene. 2000 Oct 26;19(45):5153-5162.
Pereno, Raffaele ; Giron-Michel, Julien ; Gaggero, Alessia ; Cazes, Eric ; Meazza, Raffaella ; Monetti, Monia ; Monaco, Eugenia ; Mishal, Zohar ; Jasmin, Claude ; Indiveri, Francesco ; Ferrini, Silvano ; Azzarone, Bruno. / IL-15/IL-15Rα intracellular trafficking in haman melanoma cells and signal transduction through the IL-15Rα. In: Oncogene. 2000 ; Vol. 19, No. 45. pp. 5153-5162.
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