B-CELL ANTIGEN RECEPTOR MOTIFS HAVE REDUNDANT SIGNALING CAPABILITIES AND BIND THE TYROSINE KINASES PTK72, LYN AND FYN

Background: The B-cell antigen receptor (BCR) is a multimeric protein complex consisting of an antigen-recognition structure (membrane immun oglobulin) and two associated proteins, Ig-alpha and Ig-beta. It has b een proposed that signalling through the BCR involves Ig-alpha and Ig- beta. Both of these proteins contain within their cytoplasmic domains an amino-acid motif that is present in a number of immune recognition receptors, including the BCR, T-cell antigen receptor and Fc receptor complexes. This motif, termed the antigen-receptor homology motif (ARH 1), appears to have signal transduction ability. Results: We now show that the presence of cytoplasmic regions containing the ARH1 motif fro m either Ig-alpha or Ig-beta is sufficient to confer signalling capabi lity on an otherwise non-functional fusion protein. Both Ig-alpha and Ig-beta-containing chimeras induced, in an apparently redundant fashio n, signalling events seen upon membrane immunoglobulin crosslinking, i ncluding tyrosine phosphorylation of particular proteins, phosphoinosi tide breakdown and calcium mobilization. Furthermore, crosslinking of the chimeras resulted in tyrosine phosphorylation of the Ig-alpha and Ig-beta tails and their association with the tyrosine kinases PTK72, p 53/56 (lym) and p59 (fyn). Conclusions: These observations indicate th at Ig-alpha and Ig-beta are responsible for coupling membrane immunogl obulin to intracellular signalling components. Moreover, they demonstr ate that a number of tyrosine kinases associate directly with the cyto plasmic domains of both Ig-alpha and Ig-beta. Stimulation of the chime ras, which results in tyrosine phosphorylation of the Ig-alpha and Ig- beta tails, is a prerequisite for some of these associations. The impl ications of these findings for the mechanism by which the BCR initiate s the signalling reactions are discussed.