UNCOUPLING ACTIVATION-DEPENDENT HS1 PHOSPHORYLATION FROM NUCLEAR FACTOR OF ACTIVATED T-CELLS TRANSCRIPTIONAL ACTIVATION IN JURKAT T-CELLS -DIFFERENTIAL SIGNALING THROUGH CD3 AND THE COSTIMULATORY RECEPTORS CD2 AND CD28
Je. Hutchcroft et al., UNCOUPLING ACTIVATION-DEPENDENT HS1 PHOSPHORYLATION FROM NUCLEAR FACTOR OF ACTIVATED T-CELLS TRANSCRIPTIONAL ACTIVATION IN JURKAT T-CELLS -DIFFERENTIAL SIGNALING THROUGH CD3 AND THE COSTIMULATORY RECEPTORS CD2 AND CD28, The Journal of immunology (1950), 161(9), 1998, pp. 4506-4512
CD3, CD2, and CD28 are functionally distinct receptors on T lymphocyte
s, Engagement of any of these receptors induces the rapid tyrosine pho
sphorylation of a shared group of intracellular signaling proteins, in
cluding Vav, Cbl, p85 phosphoinositide 3-kinase, and the Src family ki
nases Lck and Fyn, Ligation of CD3 also induces the tyrosine phosphory
lation of HS1, a 75-kDa hematopoietic cell-specific intracellular sign
aling protein of unknown function, We have examined changes in HS1 pho
sphorylation after differential stimulation of CD3, CD2, and CD28 to e
lucidate its role in T cells and to further delineate the signaling pa
thways recruited by these receptors, Unlike ligation of CD3, stimulati
on with anti-CD28 mAb or CHO cells expressing the CD28 ligands CD80 or
CD86 did not lead to tyrosine phosphorylation of HS1 in Jurkat T cell
s, Additionally, no tyrosine phosphorylation of HS1 was induced by mit
ogenic pairs of anti-CD2 mAbs capable of activating the transcription
factor NFAT (nuclear factor of activated T cells), Costimulation throu
gh CD28 and/or CD2 did not modulate the CD3-dependent phosphorylation
of HS1, Ln vivo studies indicated that CD3-induced HS1 phosphorylation
was dependent upon both the Src family tyrosine kinase Lck and the ty
rosine phosphatase CD45, did not require MEK1 kinase activity, and was
regulated by protein kinase C activation, Thus, although CD3., CD28,
and CD2 activate many of the same signaling molecules, they differed i
n their capacity to induce the tyrosine phosphorylation of HS1. Furthe
rmore, activation-dependent tyrosine phosphorylation of HS1 was not re
quired for NEAT transcriptional activation.