c-Met must translocate to the nucleus to initiate calcium signals

Dawidson A. Gomes, Michele A. Rodrigues, M. Fatima Leite, Marcus V. Gomez, Peter Varnai, Tamas Balla, Anton M. Bennett, Michael H. Nathanson

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Abstract

Hepatocyte growth factor (HGF) is important for cell proliferation, differentiation, and related activities. HGF acts through its receptor c-Met, which activates downstream signaling pathways. HGF binds to c-Met at the plasma membrane, where it is generally believed that c-Met signaling is initiated. Here we report that c-Met rapidly translocates to the nucleus upon stimulation with HGF. Ca2+ signals that are induced by HGF result from phosphatidylinositol 4,5-bisphosphate hydrolysis and inositol 1,4,5-trisphosphate formation within the nucleus rather than within the cytoplasm. Translocation of c-Met to the nucleus depends upon the adaptor protein Gab1 and importin β1, and formation of Ca2+ signals in turn depends upon this translocation. HGF may exert its particular effects on cells because it bypasses signaling pathways in the cytoplasm to directly activate signaling pathways in the nucleus.

Original languageEnglish
Pages (from-to)4344-4351
Number of pages8
JournalJournal of Biological Chemistry
Volume283
Issue number7
DOIs
Publication statusPublished - Feb 15 2008

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Gomes, D. A., Rodrigues, M. A., Leite, M. F., Gomez, M. V., Varnai, P., Balla, T., Bennett, A. M., & Nathanson, M. H. (2008). c-Met must translocate to the nucleus to initiate calcium signals. Journal of Biological Chemistry, 283(7), 4344-4351. https://doi.org/10.1074/jbc.M706550200