Differential binding activity of ARH1/TAM motifs.
T- and B-cell antigen receptors, and certain receptors for IgG and IgE constant regions, transduce signals via a conserved amino acid sequence motif, termed ARH1 or TAM. Receptor ligation leads to phosphorylation of 2 tyrosines found within the motif and this phosphorylation appears critical for signal transduction. Although this 26-residue motif exhibits some functional redundancy, its variability in sequence and occurrence in multiple forms in individual receptor complexes, e.g., as many as 8 copies in TCR, suggests that individual ARH1 motifs may exhibit partially unique function. To begin to address this possibility, we compared the binding activity of doubly phosphorylated and non-phosphorylated Ig alpha, Ig beta, TcR zeta c and CD3 epsilon ARH1 motifs. Results demonstrate a clear difference in binding activity determined by both motif phosphorylation and primary structure. Among non-phosphorylated motifs, Ig alpha exhibits the most readily detectable binding activity; binding src-family kinases [1], CD22, MAPK, PI3-k, and Shc, but not CD19. Among doubly phosphorylated motifs, Ig alpha, Ig beta, TCR zeta c and CD3 epsilon all exhibit binding activity but have distinct effector preferences. For example, while Ig alpha prefers src-family kinases over the Syk kinase and binds Shc avidly, CD3 epsilon prefers Syk over src-kinases and does not bind Shc. TCR zeta c seems to bind Syk, src-kinases and Shc. These data are consistent with the possibility that ARH1 motifs may be coupled to distinct signal propagation mechanisms.
Cambier
J C
JC
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA.
Johnson
S A
SA
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism*; D001483:Base Sequence; D008214:Lymphocytes / Q000276:immunology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011946:Receptors, Antigen / Q000378:metabolism*; D011961:Receptors, Fc / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D015703:Antigens, CD; D010446:Peptide Fragments; D011946:Receptors, Antigen; D011961:Receptors, Fc; D017455:Receptors, IgE; D017452:Receptors, IgG; D011505:Protein-Tyrosine Kinases