The alpha/beta sheath and its cytoplasmic tyrosines are required for signaling by the B-cell antigen receptor but not for capping or for serine/threonine-kinase recruitment.
The B-cell antigen receptor is composed of membrane immunoglobulin sheathed by an alpha/beta heterodimer. The complex is noncovalently associated with protein kinase activity, and crosslinking of the receptor leads to capping and transmembrane signaling. Here we show that the sheath is not necessary either for this capping or for the association of membrane immunoglobulin with the detergent-insoluble cytoskeletal fraction that occurs following crosslinking. It is also not required for association of membrane immunoglobulin with a casein-kinase-like serine/threonine kinase. The sheath is essential, however, for transmembrane signaling. Provision of just the cytoplasmic domain of the beta sheath polypeptide to a mutant, unsheathed IgM molecule was sufficient to restore full signaling capability as judged by the phosphorylation of a variety of cellular proteins, including the B-cell-specific transmembrane protein CD22. This signaling was destroyed by mutating one of the tyrosines in the beta cytoplasmic domain. These results not only suggest that receptor signaling is mediated through phosphorylation of the tyrosines in the sheath's cytoplasmic domains but, together with previous work, indicate that different motifs within the sheath mediate presentation and signaling.
Williams
G T
GT
Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
Peaker
C J
CJ
Patel
K J
KJ
Neuberger
M S
MS
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003432:Cross-Linking Reagents; D003593:Cytoplasm / Q000276:immunology; D007152:Immunologic Capping; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D014162:Transfection; D014443:Tyrosine / Q000737:chemistry / Q000235:genetics
D003432:Cross-Linking Reagents; D011947:Receptors, Antigen, B-Cell; D014443:Tyrosine; D017346:Protein Serine-Threonine Kinases