Loss of the exon encoding the juxtamembrane domain is essential for the oncogenic activation of TPR-MET.
In: Oncogene, Jg. 18 (1999-07-22), Heft 29, S. 4275-4281
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Zugriff:
TPR-MET:, a transforming counterpart of the c-MET proto-oncogene detected in experimental and human cancer, results from fusion of the MET kinase domain with a dimerization motif encoded by TPR. In this rearrangement the exons encoding the Met extracellular, transmembrane and juxtamembrane domains are lost. The juxtamembrane domain has been suggested to be a regulatory region endowed with negative feedback control. To understand whether its absence is critical for the generation of the Tpr-Met transforming potential, we produced a chimeric molecule (Tpr-juxtaMet) with a conserved juxtamembrane domain. The presence of the domain (aa 962–1009) strongly inhibited Tpr-Met dependent cell transformation. Cell proliferation, anchorage-independent growth, motility and invasion were also impaired. The enzymatic behavior of Tpr-Met and Tpr-juxtaMet was the same, while Tpr-juxtaMet ability to associate cytoplasmic signal transducers and to elicit downstream signaling was severely impaired. These data indicate that the presence of the juxtamembrane domain counterbalances the Tpr-Met transforming potential and therefore the loss of the exon encoding the juxtamembrane domain is crucial in the generation of the active TPR-MET oncogene. [ABSTRACT FROM AUTHOR]
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Loss of the exon encoding the juxtamembrane domain is essential for the oncogenic activation of TPR-MET.
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Autor/in / Beteiligte Person: | Vigna, Elisa ; Gramaglia, Daniela ; Longati, Paola ; Bardelli, Alberto ; Comoglio, Paolo M |
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Zeitschrift: | Oncogene, Jg. 18 (1999-07-22), Heft 29, S. 4275-4281 |
Veröffentlichung: | 1999 |
Medientyp: | academicJournal |
ISSN: | 0950-9232 (print) |
DOI: | 10.1038/sj.onc.1202791 |
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