Expression of the human epidermal growth factor receptor in a murine T-cell hybridoma. A transmembrane protein tyrosine kinase can synergize with the T-cell antigen receptor.
Although the T-cell receptor for antigen (TCR) lacks intrinsic kinase activity, stimulation of this receptor induces tyrosine phosphorylation of multiple substrates. In contrast, the epidermal growth factor receptor (EGFR) has intrinsic cytoplasmic tyrosine kinase catalytic activity that is activated upon EGF binding. To compare the functional effects of the TCR and a transmembrane protein tyrosine kinase (PTK), we used retrovirus-mediated gene transduction to express the human c-erbB proto-oncogene, encoding the EGFR, in a murine T-cell hybridoma. Tyrosine phosphorylation induced by the TCR and the EGFR occurred on substrates unique to each receptor as well as on several shared substrates, including the zeta chain of the TCR. Stimulation of the EGFR induced calcium ion flux in these cells, suggesting that the heterologous tyrosine kinase can couple to the T-cell phospholipase signal transduction pathway, but this stimulus did not lead to interleukin 2 production. However, EGF stimulation of transduced cells significantly enhanced TCR signaling, as assessed by interleukin 2 production, indicating that cross talk can occur between the TCR and a transmembrane PTK.
Kennedy
I C
IC
Laboratory of Experimental Immunology, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201.
June
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CH
O'Shea
J J
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D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D004247:DNA / Q000235:genetics; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D006825:Hybridomas / Q000378:metabolism*; D007376:Interleukin-2 / Q000096:biosynthesis; D051379:Mice; D010766:Phosphorylation; D010957:Plasmids; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D014161:Transduction, Genetic
D007376:Interleukin-2; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D004815:Epidermal Growth Factor; D004247:DNA; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D002118:Calcium