Priming of CD2-induced p62Dok tyrosine phosphorylation by CD3 in Jurkat T cells.
T lymphocyte activation is triggered through the CD3-TCR complex or the CD2 molecule. Beside common biochemical events, we previously showed that a 62-kDa protein associated with PLCgamma-1 and p21RasGAP was specifically tyrosine phosphorylated after CD2 stimulation in Jurkat T cells. We demonstrated here that it was identical to p62Dok, a docking protein highly phosphorylated in human chronic myelogenous leukemia cells and in murine abl-transformed B cells. Mainly, we showed that p62Dok tyrosine phosphorylation was strengthened by the functional interplay between CD3 and CD2. Primary stimulation of Jurkat cells via CD3 suppressed most of the subsequent CD2-dependent phosphorylation events, except p62Dok tyrosine phosphorylation, which was on the contrary strongly increased. Kinetic studies indicated that a short treatment with anti-CD3 was sufficient to amplify the CD2-induced tyrosine phosphorylation of p62Dok. By contrast, CD2-induced PLCgamma-1 tyrosine phosphorylation and calcium response progressively diminished. Finally, enhanced amounts of tyrosine phosphorylated p62Dok were recruited to p21RasGAP and PLCgamma-1 after CD2 stimulation in CD3-activated cells. CD3 stimulation is known to enhance CD2 avidity for its ligand and to induce the binding of the CD2AP protein to the CD2 cytoplasmic tail. Our results suggest that the CD3-TCR complex rapidly primes the CD2 pathway to activate one of its specific components, p62Dok.
Harriague
J
J
Laboratoire d'Immunologie Cellulaire, CNRS UMR 7627, Hôpital Pitié-Salpêtrière, Paris, France.
Debré
P
P
Bismuth
G
G
Hubert
P
P
D018801:CD2 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D004268:DNA-Binding Proteins; D006801:Humans; D019169:Jurkat Cells; D010750:Phosphoproteins / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation; D016601:RNA-Binding Proteins; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014443:Tyrosine / Q000276:immunology / Q000378:metabolism
D018801:CD2 Antigens; D017252:CD3 Complex; D004268:DNA-Binding Proteins; C489560:DOK1 protein, human; C074561:GAP-associated protein p62; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D014443:Tyrosine