title: T cell regulation of p62(dok) (Dok1) association with Crk-L.
abstract: 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 approximately 50-kDa 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, p62(dok) (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 p62(dok) 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 p62(dok). While CD2-induced p62(dok) tyrosine phosphorylation was independent of both the p36/38 membrane adapter protein linker of activated T cells (LAT) and the ZAP70/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 p62(dok) to Crk-L. The CD2-dependent association of p62(dok) to Crk-L was independent of expression of the ZAP70/Syk family of kinases. Of note, while T cell receptor-CD3 engagement did not induce either p62(dok) phosphorylation or Crk-L association in Jurkat T cells, it did inhibit CD2-dependent p62(dok)-Crk-L complexes; this TcR-CD3-mediated regulation was dependent upon ZAP70 kinase activity. Our data suggest that phosphorylation of p62(dok) and its interaction with other signaling proteins may depend upon integrated signals emanating from the CD2 receptor, utilizing a ZAP70/LAT-independent pathway, and the TcR-CD3 receptor, which is ZAP70/Syk-dependent.
authors.affiliation: Laboratory of Lymphocyte Biology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Martelli
authors.forename: J
authors.initials: J
authors.lastname: Boomer
authors.forename: M
authors.initials: M
authors.lastname: Bu
authors.forename: B E
authors.initials: BE
authors.lastname: Bierer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D018801:CD2 Antigens / Q000378:metabolism; D004268:DNA-Binding Proteins; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D009687:Nuclear Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016601:RNA-Binding Proteins; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D000072377:Syk Kinase; D013601:T-Lymphocytes / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D051746:ZAP-70 Protein-Tyrosine Kinase
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018801:CD2 Antigens; C082869:CRKL protein; D004268:DNA-Binding Proteins; C489560:DOK1 protein, human; D004792:Enzyme Precursors; C074561:GAP-associated protein p62; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D011948:Receptors, Antigen, T-Cell; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human