from 11/1 issue of JI.....
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 CD281
Jill E. Hutchcroft,2* Jacqueline M. Slavik,* Huamao Lin,* Takeshi Watanabe,† and Barbara E. Bierer3*‡
*Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115; †Department of Molecular Immunology,
Kyushu University, Fukuoka, Japan; and ‡Department of Pediatrics and Medicine, Harvard Medical School, Boston, MA 02115
The Journal of Immunology, 1998, 161: 4506-4512.
CD3, CD2, and CD28 are functionally distinct receptors on T lymphocytes. Engagement of any of these receptors induces the rapid
tyrosine phosphorylation of a shared group of intracellular signaling proteins, including Vav, Cbl, p85 phosphoinositide 3-kinase, and
the Src family kinases Lck and Fyn. Ligation of CD3 also induces the tyrosine phosphorylation of HS1, a 75-kDa hematopoietic
cell-specific intracellular signaling protein of unknown function. We have examined changes in HS1 phosphorylation after
differential stimulation of CD3, CD2, and CD28 to elucidate its role in T cells and to further delineate the signaling pathways
recruited by these receptors. Unlike ligation of CD3, stimulation 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 cells. Additionally, no tyrosine phosphorylation of HS1
was induced by mitogenic pairs of anti-CD2 mAbs capable of activating the transcription factor NFAT (nuclear factor of activated
T cells). Costimulation through CD28 and/or CD2 did not modulate the CD3-dependent phosphorylation of HS1. In vivo studies
indicated that CD3-induced HS1 phosphorylation was dependent upon both the Src family tyrosine kinase Lck and the tyrosine
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 in their capacity to induce the tyrosine phosphorylation
of HS1. Furthermore, activation-dependent tyrosine phosphorylation of HS1 was not required for NFAT transcriptional activation. |
