Sequential interactions of the TCR with two distinct cytoplasmic tyrosine kinases.
The T cell antigen receptor (TCR) initiates signals by interacting with cytoplasmic protein tyrosine kinases (PTKs) through a 17-residue sequence motif [called the antigen recognition activation motif (ARAM)] that is contained in the TCR zeta and CD3 chains. TCR stimulation induces the tyrosine phosphorylation of several cellular substrates, including the ARAMs. Lck kinase activity is required for phosphorylation of two conserved tyrosine residues in an ARAM. This phosphorylation leads to the recruitment of a second cytoplasmic PTK, ZAP-70, through both of the ZAP-70 Src homology 2 domains and its phosphorylation. Thus, TCR signal transduction is initiated by the sequential interaction of two PTKs with TCR ARAMs.
Iwashima
M
M
Howard Hughes Medical Institute, University of California, San Francisco 94143.
Irving
B A
BA
van Oers
N S
NS
Chan
A C
AC
Weiss
A
A
D000595:Amino Acid Sequence; D000818:Animals; D016827:CD8 Antigens / Q000378:metabolism; D002460:Cell Line; D003593:Cytoplasm / Q000201:enzymology; D000882:Haplorhini; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D051746:ZAP-70 Protein-Tyrosine Kinase
D016827:CD8 Antigens; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human