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Papers In Press, published online ahead of print September 11, 2001
Laboratory of Lymphocyte Biology, National Institutes of Health, NHLBI, Bethesda, MD 20892
Corresponding Author: BiererB{at}nih.gov
In addition to engagement of the T cell receptor-CD3 complex, T lymphocytes can be activated by a variety of cell surface molecules including the ~50kD surface receptor CD2. While the majority of biochemical signaling elements are triggered by either CD2 or TcR-CD3 receptors, a small number of proteins are engaged by only one receptor. Recently, p62dok (Dok1), a member of the Dok family of adapter molecules, has been reported to be activated by CD2 and not by CD3 engagement. Here we have examined the role of p62dok in CD2-dependent signaling in Jurkat T cells. As previously reported, we find that ligation of the CD2 molecule by mitogenic pairs of anti-CD2 mAbs led to phosphorylation of p62dok. While CD2-induced p62dok tyrosine phosphorylation was independent of both the p36/38 membrane adapter protein linker of activated T cells (LAT) and the ZAP-70/Syk family of kinases, it was dependent upon the Src-family of kinases including Lck and Fyn. We find further that CD2 engagement induced the association of tyrosine phosphorylated p62dok to Crk-L. The CD2-dependent association of p62dok to Crk-L was independent of expression of the ZAP-70/Syk family of kinases. Of note, while T cell receptor-CD3 engagement did not induce either p62dok phosphorylation or Crk-L association in Jurkat T cells, it did inhibit CD2-dependent p62dok-Crk-L complexes; this TcR-CD3-mediated regulation was dependent upon ZAP-70 kinase activity. Our data suggest that phosphorylation of p62dok and its interaction with other signaling proteins may depend upon integrated signals emanating from the CD2 receptor, utilizing a ZAP-70/LAT-independent pathway, and the TcR-CD3 receptor, which is ZAP-70/Syk-dependent.
J. Biol. Chem, 10.1074/jbc.M105777200
Submitted on June 21, 2001
Revised on September 10, 2001
Accepted on September 11, 2001
T cell regulation of p62dok (Dok1) association with Crk-L
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