Redox mechanism as alternative to ligand binding for receptor activation delivering disregulated cellular signals

Izumi Nakashima, Mei Yi Pu, Akira Nishizaki, Idris Rosila, Li Ma, Yoshiaki Katano, Kozo Ohkusu, S. M.Jamshedur Rahman, Ken Ichi Isobe, Michinari Hamaguchi, Keisuke Saga

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106 Citations (Scopus)

Abstract

Cross-linking with specific ligand is a general requirement for ordered activation of cell surface receptors. In this study we demonstrated a novel pathway for disregulated receptor activation through a redox mechanism. Treatment of murine thymocytes or spleen cells with thiol-reactive HgCl2, a known inducer of autoimmune proliferative lymphocyte disorders in rodents, was found to induce tyrosine phosphorylation of several cellular proteins, which was up to 100 times as extensive as that triggered by stimulation with antireceptor antibody or mitogen. Through the cross-linkage by thiol-reactive bivalent mercury, transmembrane CD4, CD3, and CD45 and glycosylphosphatidylinositol-anchored Thy-1 were aggregated together on thymocytes or T lymphocytes. Along with the aggregation of Thy-1 and CD4, nonreceptor protein tyrosine kinase p56(lck) was aggregated and activated. These events were linked to extensive protein tyrosine phosphorylation, which was visualized as a well localized spot beneath the membrane. Under appropriate conditions, this novel pathway of multiple receptor aggregation delivered a disregulated signal into T lymphocytes, which cross-talked to the antireceptor antibody-induced signal, for prolonged cell proliferation and IL-2 production. These results suggest a novel mechanism of disregulation of the ligand-dependent receptor function.

Original languageEnglish
Pages (from-to)1064-1071
Number of pages8
JournalJournal of Immunology
Volume152
Issue number3
Publication statusPublished - 01-02-1994

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Nakashima, I., Pu, M. Y., Nishizaki, A., Rosila, I., Ma, L., Katano, Y., Ohkusu, K., Rahman, S. M. J., Isobe, K. I., Hamaguchi, M., & Saga, K. (1994). Redox mechanism as alternative to ligand binding for receptor activation delivering disregulated cellular signals. Journal of Immunology, 152(3), 1064-1071.