Role of tyrosine kinases in lymphocyte activation.
Interaction of T- and B-cell antigen receptors with cytoplasmic non-receptor tyrosine protein kinases is critical to the activation of lymphocytes by antigen. Both the src-family tyrosine protein kinases Lck, Fyn, Lyn and Blk and the syk-family tyrosine protein kinases Syk and ZAP-70 play a role in lymphocyte activation. The antigen receptors are coupled to this cluster of kinases by the cytoplasmic tails of the gamma, delta, epsilon, zeta, and eta subunits of the T-cell receptor, and the Ig-alpha and Ig-beta subunits of the B-cell receptor. Each of these proteins contains one or more 'tyrosine based activation motifs', with the amino acid sequence D/EX7D/EXXYXXL/IX7YXXL/I. This motif appears to allow binding of one or more src-like kinases, via their unique amino termini, before the onset of lymphocyte activation. Invariant tyrosines in the motif become phosphorylated following the triggering of lymphocyte activation, and this modification induces the binding of the src- and syk-family tyrosine protein kinases, and potentially other signalling molecules, through SH2 domains to the antigen receptors.
Sefton
B M
BM
Molecular Biology and Virology Laboratory, Salk Institute, San Diego, California 92186.
Taddie
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D016384:Consensus Sequence; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000502:physiology; D015398:Signal Transduction
D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases