J. Biol. Chem., Vol. 265, Issue 17, 10138-10142, 06, 1990
Stimulation of the antigen and interleukin-2 receptors on T lymphocytes activates distinct tyrosine protein kinases
EM Saltzman, K White and JE Casnellie
Department of Pharmacology, University of Rochester Medical Center, New York 14642.
The T cell antigen receptor complex (TCR) and the interleukin 2 (IL-2)
receptor are responsible for signal transduction that results in T
lymphocyte activation and proliferation. Stimulation of either the TCR or
the IL-2 receptor induces an increase in tyrosine phosphorylation of
several cellular proteins indicating that signal transduction by both of
these receptors involves the activation of a tyrosine protein kinase.
Although the tyrosine protein kinases activated by these receptors have not
yet been characterized the receptors themselves are known not to contain a
tyrosine protein kinase domain. To determine if these receptors are coupled
to the activation of similar or distinct tyrosine protein kinases we
examined the patterns and kinetics of tyrosine phosphorylation induced by
stimulation of these receptors on a cloned cell line. Hut 78.3 cells
co-express the TCR and the p75 IL-2 receptor. These cells were stimulated
with either OKT3 antibodies, specific for the TCR, or with IL-2. Signal
transduction by these receptors was found to increase the tyrosine
phosphorylation of a set of proteins unique to each stimulus. The kinetics
of the tyrosine phosphorylation induced by OKT3 antibodies also differed
from that induced by IL-2. The OKT3-dependent tyrosine phosphorylation
reached maximal levels within 2.5 min and began to decline by 5 min after
stimulation. In contrast, the IL-2-induced tyrosine phosphorylation did not
achieve maximal levels until 15 min after the addition of IL-2 and the
proteins remained phosphorylated even after 60 min of incubation. In
addition the tyrosine phosphorylations induced by OKT3 and IL-2 were not
affected by prior stimulation with the other agent. These results
demonstrate that the TCR and IL-2 receptor are coupled to different signal
transduction pathways responsible for the independent activation of
distinct tyrosine protein kinases.