Tyrosine phosphorylation and recruitment of ZAP-70 to the CD3-TCR complex are defective after CD2 stimulation.
CD2 has been described as an alternative transduction pathway sharing the same biochemical cascade as CD3. The T cell-specific protein tyrosine kinase (PTK) ZAP-70 is believed to play a key role in early tyrosine phosphorylations of cellular proteins induced by CD3 stimulation. We show in the present report that ZAP-70 is insignificantly tyrosine phosphorylated and recruited to CD3 after CD2 stimulation in Jurkat T cells. The same result is obtained for p72syk, a PTK structurally and functionally related to ZAP-70. Several studies have suggested a model in which p56lck would be responsible after CD3 triggering for the phosphorylation of particular tyrosine residues in the immunoreceptor tyrosine-based activation motifs of the CD3 chains, inducing the recruitment and the tyrosine phosphorylation of ZAP-70. In Jurkat cells, p56lck is required for CD3- or CD2-induced tyrosine phosphorylations and clearly activated after CD2 cross-linking. However, we find that the CD3 complex, and especially its zeta-chain, are faintly tyrosine phosphorylated after CD2 triggering. By contrast, CD2 induces PLCgamma-1 tyrosine phosphorylation as efficiently as CD3, with a correlated inositol phosphate production and intracellular calcium increase, and even a higher production of IL-2. Interestingly, the SH2 domains of PLCgamma-1 associate with ZAP-70 upon CD3 stimulation while they bind, in CD2-activated cells, to a heavily tyrosine-phosphorylated 62-kDa protein. Altogether, these findings suggest that CD2 could bypass the PTK ZAP-70 for PLCgamma-1 activation and involves a preferential cascade comprising p56lck and a p62 protein, possibly acting as an anchor molecule.
Hubert
P
P
Laboratory of Cellular and Tissue Immunology, CNRS URA 625, Paris, France.
Lang
V
V
Debré
P
P
Bismuth
G
G
D018801:CD2 Antigens / Q000502:physiology*; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D000072377:Syk Kinase; D010738:Type C Phospholipases / Q000187:drug effects; D051746:ZAP-70 Protein-Tyrosine Kinase; D018909:src Homology Domains / Q000187:drug effects; D019061:src-Family Kinases / Q000378:metabolism
D018801:CD2 Antigens; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; C000606896:SYK protein, human; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D019061:src-Family Kinases; D010738:Type C Phospholipases