Differential Ras signaling via the antigen receptor and IL-2 receptor in primary T lymphocytes.
Ras can become activated via multiple distinct receptors in T lymphocytes. However, mechanistic studies of Ras signaling in normal T cells have been hampered by the lack of an efficient technology for gene transfer into resting post-thymic cells. We have overcome this limitation by utilizing adenoviral transduction of T cells from Coxsackie/adenovirus receptor transgenic mice. Unexpectedly, dominant negative Ras17N blocked activation of Ras and ERK in response to IL-2R engagement but not TCR/CD3 ligation. However, TCR-induced ERK activation was suppressed by inhibitors of PKC and PLC-gamma. This first biochemical study of DN Ras in normal quiescent T cells reveals a striking contrast in Ras signaling via two receptors, and suggests that the principal mechanism of TCR-induced Ras activation in normal T cells may be distinct from that utilized in T-lineage tumor cell lines.
Marks
Reinhard E
RE
Department of Pathology, Department of Medicine Section of Hematology/Oncology, The Ben May Institute for Cancer Research, University of Chicago, Chicago, IL 60637, USA.
Ho
Allen W
AW
Rivas
Fabiola
F
Marshall
Emily
E
Janardhan
Sujit
S
Gajewski
Thomas F
TF
D000818:Animals; D004789:Enzyme Activation; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016716:PC12 Cells; D010766:Phosphorylation; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism*
D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins