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Cell‐to‐cell transfer of the G protein Ras at the immunological synapse
Author(s) -
Rechavi Oded,
Vernitsky Helly,
Rotblat Barak,
Kloog Yoel,
Goldstein Itamar
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1064.7
Subject(s) - immunological synapse , microbiology and biotechnology , cell , cell signaling , flow cytometry , intracellular , biology , chemistry , signal transduction , t cell , immune system , immunology , biochemistry , t cell receptor
Immune cells establish dynamic adhesive cell–cell interactions at a specific contact region, termed the immunological synapse (IS). Important features of the IS are the formation of cell‐cell membrane bridges and the exchange of selected cell surface proteins between conjugated cells. In this study we investigated whether upon IS formation, inner plasma membrane associated G‐proteins can also transfer from target cells to lymphocytes and transmit signals across cell boundaries. Here we show by flow cytometry and confocal microscopy that human NK and T cells rapidly acquire from the cells they scan, in a contact dependent manner, the intracellular G‐protein Ras: a signal transducing protein vital for common lymphocyte functions and a prominent participant in human cancer. Importantly, we also show that the transfer of the constitutively active oncogenic mutant of H‐Ras, H‐RasG12V, from 721.221 transfectants to NK cells had significant biological effects. The transfer correlated with augmented ERK phosphorylation and interferon‐γ production in the adopting NK cells as well as increased target cell killing. These findings reveal a hitherto undescribed mode of cell‐to‐cell communication that enhances the capacity of lymphocytes to probe and react to the proteome of the cells they survey, and that may moreover play an important role in natural tumor immunity.