Signal transduction by the cytoplasmic domains of Fc epsilon RI-gamma and TCR-zeta in rat basophilic leukemia cells.
The gamma subunit of the high affinity IgE receptor, Fc epsilon RI, is a member of a family of proteins which form disulfide-linked dimers. This family also includes the zeta- and eta-chains of the T cell receptor. Engagement of Fc epsilon RI activates src-related protein tyrosine kinases in basophils and mast cells. However, the role of individual subunits of Fc epsilon RI in this activation is still not known. In an effort to determine the function of Fc epsilon RI-gamma, we used chimeric proteins containing the extracellular and transmembrane domains of the alpha chain of the human interleukin 2 receptor (Tac) and the cytoplasmic domains of either T cell receptor-zeta or Fc epsilon RI-gamma. We show that while cross-linking of the Tac chimeras in the rat basophilic leukemia cell line RBL-2H3 resulted in the tyrosine phosphorylation of a subset of proteins and a portion of the degranulation normally observed after Fc epsilon RI-mediated stimulation, no detectable activation of p56lyn or pp60c-src was observed. In contrast, an apparent transient deactivation of these two kinases was observed after Tac chimera cross-linking. These observations suggest that Fc epsilon RI-gamma is responsible for some, but not all, of the signaling that occurs after engagement of its receptor, and that other receptor subunits may also play important roles in this signaling process.
Eiseman
E
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Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543.
Bolen
J B
JB
D000818:Animals; D000911:Antibodies, Monoclonal; D002462:Cell Membrane / Q000502:physiology; D007700:Kinetics; D015471:Leukemia, Basophilic, Acute; D046911:Macromolecular Substances; D019000:Phosphotyrosine; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000032:analysis / Q000502:physiology*; D017455:Receptors, IgE / Q000032:analysis / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D000911:Antibodies, Monoclonal; D046911:Macromolecular Substances; D011948:Receptors, Antigen, T-Cell; D017455:Receptors, IgE; D011993:Recombinant Fusion Proteins; D019000:Phosphotyrosine; D012701:Serotonin; D014443:Tyrosine; D016392:Proto-Oncogene Proteins pp60(c-src)