Membrane IgM-induced tyrosine phosphorylation of CD19 requires a CD19 domain that mediates association with components of the B cell antigen receptor complex.
CD19 enhances membrane IgM (mIgM) signaling and is required for B lymphocyte responses to T-dependent Ags. CD19 is tyrosine phosphorylated when mIgM is ligated and binds SH2 domain-containing signaling proteins. We suggest that the basis for phosphorylation is the association of CD19 with Syk and other components of the mIgM complex. IgM, CD22, Ig-alpha, Ig-beta, and Syk were coimmunoprecipitated with CD19 from detergent lysates of B lymphocytes. The association was maintained with a chimeric form of CD19 containing only the transmembrane domain and the membrane proximal 17 amino acids of the cytoplasmic domain encoded by exon 6. This sequence is sufficient to mediate the association, as a synthetic peptide of the exon 6-encoded region adsorbs IgM and Syk. Deletion of the juxtamembrane 17 amino acids of the cytoplasmic domain encoded by CD19 exon 6 abolishes association of CD19 with the mIgM complex. Deletion of these amino acids, which contain no tyrosines, also reduces mIgM-induced tyrosine phosphorylation of the remainder of the CD19 cytoplasmic domain. Coligating this mutant CD19 to mIgM restores phosphorylation. Thus, a discrete region of the cytoplasmic domain regulates the tyrosine phosphorylation of CD19 in the activation of B cells by mIgM.
Carter
R H
RH
Department of Medicine, University of Alabama at Birmingham, 35294, USA.
Doody
G M
GM
Bolen
J B
JB
Fearon
D T
DT
D000595:Amino Acid Sequence; D018941:Antigens, CD19 / Q000235:genetics / Q000502:physiology*; D001345:Autoradiography; D006801:Humans; D007075:Immunoglobulin M / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism* / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D015398:Signal Transduction / Q000276:immunology; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*
D018941:Antigens, CD19; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; D014443:Tyrosine