Association of Src-family kinase Lyn with B-cell antigen receptor.

Antigen is thought to cross-link membrane-bound immunoglobulins (Igs) of B cells, causing proliferation and differentiation or the inhibition of growth. Compelling evidence suggests that protein-tyrosine phosphorylation is involved in signal transduction for cell proliferation and differentiation. Indeed cross-linking of membrane-bound IgM (mIgM) induced a rapid increase in tyrosine phosphorylation of at least 10 distinct proteins in B cells. The Src-family protein tyrosine kinase Lyn (p56lyn and p53lyn) is expressed preferentially in B cells. The Lyn protein and its kinase activity could be coimmunoprecipitated with both IgM and IgD from detergent lysates. Cross-linking of membrane-bound IgM with antibody induced down-regulation of the Lyn protein. From these data we concluded that Lyn is physically associated with mIgs. Further evidence showed that cross-linking of mIgM induced rapid increase in the kinase activity of Lyn and association of Lyn with 85-kDa noncatalytic subunit of phosphatidylinositol 3-kinase. Thus, Lyn is likely to participate in B-cell antigen receptor-mediated signaling. As a novel signaling molecule downstream of Lyn, we identified src homology 3-containing, transcription factor-like molecule p75HS1.